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Soltani M, Soltani M, Karami-Mohajeri S, Mohadesi A, Ranjbar M, Oghabian Z, Mehrpour O, Khosravi F. An interdisciplinary approach to assessing the toxicity reduction of cerium oxide nanoparticles coated with polyethylene glycol and polyvinylpyrrolidone polymers: An in vitro study. Toxicol In Vitro 2025; 105:106022. [PMID: 39986636 DOI: 10.1016/j.tiv.2025.106022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 01/18/2025] [Accepted: 02/07/2025] [Indexed: 02/24/2025]
Abstract
OBJECTIVE This study combines toxicology, analytical chemistry, and nanotechnology to develop cerium oxide nanoparticles, both uncoated and coated with Polyethylene Glycol and Polyvinylpyrrolidone polymers. The objective is to assess their toxicity reduction using cell-based assays. METHODS Nanoparticles were synthesized using the co-precipitation technique. Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were employed to characterize their properties. The MTT assay evaluated cell viability, whereas reactive oxygen species and LPO assays were used to quantify oxidative stress. FINDINGS The chemical analysis of nanoparticles of the study revealed that cerium oxide nanoparticles exhibited better and more regular morphological characteristics compared to nanoparticles coated with PEG and PVP polymers in terms of size. In addition, cerium oxide nanoparticles combined with PVP polymer did not retain the morphology at the nano level. Toxicological studies demonstrated a reduction in the toxicity of cerium oxide nanoparticles when coated with PEG and PVP polymers. DISCUSSION AND CONCLUSION The study found that PEG coating significantly reduces the cytotoxicity of cerium oxide nanoparticles more effectively than PVP coating by mitigating oxidative stress. This approach presents a promising strategy for developing safer cerium oxide-based products for pharmaceutical and medical applications.
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Affiliation(s)
- Mohadeseh Soltani
- Department of Chemistry, Faculty of Science, Shahid Bahonar University of Kerman, 76175-14111 Kerman, Iran
| | - Motahareh Soltani
- Pistachio Safety Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Somayyeh Karami-Mohajeri
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran; Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
| | - Alireza Mohadesi
- Department of Chemistry, Payame Noor University, Tehran 19395-4697, Iran
| | - Mehdi Ranjbar
- Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
| | - Zohreh Oghabian
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Omid Mehrpour
- Michigan Poison & Drug Information Center, School of Medicine, Wayne State University, Detroit, MI 48202, USA
| | - Farshid Khosravi
- Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
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Almarshad HA, Elderdery A, Alenazy FO, Elissidig SA. Impact of Gold Nanoparticles Intraperitoneal Injection on Mice's Erythrocytes and Renal Tissue. IEEE Trans Nanobioscience 2025; 24:174-179. [PMID: 39361453 DOI: 10.1109/tnb.2024.3471813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/05/2024]
Abstract
The purpose of this study was to investigate the effects of two different types of gold nanoparticles (AuNPs) delivered by intraperitoneal (IP) injection on blood and kidney tissue changes in a mouse model. Three groups of fifteen adult male BALB/c healthy mice, weighing approximately 25- 30 g, were used for the experiment and designated G1, G2, and G3, respectively. G1 mice received vehicle, whereas G2 and G3 received an IP injection of 10 mg/kg body weight of methoxy poly ethylene glycol gold nanoparticles (PEG-AuNPs) and fluorescently dye labeled gold nanoparticles (Dye-AuNPs), respectively. Hematological parameters were measured based on the standard complete blood cell count (CBC) technique. The two nanoparticles, i.e., PEG-AuNPs and Dye-AuNPs, significantly reduced most red blood cell (RBC) parameters in the groups with the exception of a nonsignificant effect on hemoglobin (HBG) levels. Both gold nanoparticles, i.e., PEG-AuNPs and Dye-AuNPs, led to a reduced RBC count, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) level when compared with the control. Notably, Dye-AuNPs and PEG-AuNPs resulted in a considerably higher RBC distribution RDW- (CV % and SD fL). Glomerular injury was suggested based on the development of hydropic degeneration and the presence of a protein-rich fluid inside the tubules. Renal tissue and blood indices changed significantly in response to the two nanoparticles, suggesting possible organ injury.
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Zhu J, Lee H, Huang R, Zhou J, Zhang J, Yang X, Zhou W, Jiang W, Chen S. Harnessing nanotechnology for cancer treatment. Front Bioeng Biotechnol 2025; 12:1514890. [PMID: 39902172 PMCID: PMC11788409 DOI: 10.3389/fbioe.2024.1514890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 12/30/2024] [Indexed: 02/05/2025] Open
Abstract
Nanotechnology has become a groundbreaking innovation force in cancer therapy, offering innovative solutions to the limitations of conventional treatments such as chemotherapy and radiation. By manipulating materials at the nanoscale, researchers have developed nanocarriers capable of targeted drug delivery, improving therapeutic efficacy while reducing systemic toxicity. Nanoparticles like liposomes, dendrimers, and polymeric nanomaterials have shown significant promise in delivering chemotherapeutic agents directly to tumor sites, enhancing drug bioavailability and minimizing damage to healthy tissues. In addition to drug delivery, with the utilization of tools such as quantum dots and nanosensors that enables more precise identification of cancer biomarkers, nanotechnology is also playing a pivotal role in early cancer detection and diagnosis. Furthermore, nanotechnology-based therapeutic strategies, including photothermal therapy, gene therapy and immunotherapy are offering novel ways to combat cancer by selectively targeting tumor cells and enhancing the immune response. Nevertheless, despite these progressions, obstacles still persist, particularly in the clinical translation of these technologies. Issues such as nanoparticle toxicity, biocompatibility, and the complexity of regulatory approval hinder the widespread adoption of nanomedicine in oncology. This review discusses different applications of nanotechnology in cancer therapy, highlighting its potential and the hurdles to its clinical implementation. Future research needs to concentrate on addressing these obstacles to unlock the full potential of nanotechnology in providing personalized, effective, and minimally invasive cancer treatments.
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Affiliation(s)
- Jiajun Zhu
- Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Shanghai Medical College, Fudan University, Shanghai, China
| | - HaeJu Lee
- Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Shanghai Medical College, Fudan University, Shanghai, China
| | - Ruotong Huang
- Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China
- Shanghai Medical College, Fudan University, Shanghai, China
| | - Jianming Zhou
- Shanghai Medical College, Fudan University, Shanghai, China
| | - Jingjun Zhang
- Department of Rehabilitation Medicine, The Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoyi Yang
- Shanghai Medical College, Fudan University, Shanghai, China
| | - Wenhan Zhou
- Shanghai Medical College, Fudan University, Shanghai, China
| | - Wangqing Jiang
- Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Shuying Chen
- Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China
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Sikora J, Błaszkiewicz P, Dudkowiak A, Jagielska J, Żurawski J. Cytotoxicity of gold nanoparticles to human lymphocytes: a comparison between rod-shaped and spherical nanoparticles. Contemp Oncol (Pozn) 2025; 28:326-334. [PMID: 39935760 PMCID: PMC11809566 DOI: 10.5114/wo.2024.146995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 10/28/2024] [Indexed: 02/13/2025] Open
Abstract
Introduction Gold nanoparticles (AuNPs) have unique properties that promise new and improved methods for targeting cancer treatment and diagnosis. However, despite their relatively high biocompatibility, AuNPs can negatively affect cell viability. Research indicates that the interactions with the plasma membrane and cellular uptake of AuNPs depend significantly on size, shape, and surface modifications. Material and methods We evaluated the use of human lymphocyte primary culture as a model for assessing the to-xicity of AuNPs in proliferating cells. We compared the toxicity of rod-shaped, PEGylated AuNPs (gold nanorods, AuNRs) of two different sizes and gold nanospheres (AuNSs). Results Our results show that at high concentrations, both AuNSs and AuNRs negatively affect the viability of activated human lymphocytes in vitro. The cytotoxic effect varies with size and concentration, with larger AuNRs (approx. 22 × 50 nm) being more toxic than smaller ones (approx. 20 × 40 nm) and 15 nm AuNSs exhibiting the lowest toxicity. Conclusions Our results confirm that the application of AuNPs in cancer the-rapy and diagnostics must be accompanied by a thorough cytotoxicity assessment. Despite certain limitations, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction test for viability assessment of proliferating cells proves to be a simple and cost-effective method useful in nanoparticle toxicity studies.
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Affiliation(s)
- Jacek Sikora
- Department of Immunobiology, Poznan University of Medical Sciences, Poznan, Poland
| | - Paulina Błaszkiewicz
- Faculty of Materials Engineering and Technical Physics, Poznan University of Technology, Poznan, Poland
| | - Alina Dudkowiak
- Faculty of Materials Engineering and Technical Physics, Poznan University of Technology, Poznan, Poland
| | - Joanna Jagielska
- Department of Bioinformatics and Computational Biology, Poznan University of Medical Sciences, Poznan, Poland
| | - Jakub Żurawski
- Department of Immunobiology, Poznan University of Medical Sciences, Poznan, Poland
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Wu H, Tang L, Dong H, Zhi M, Guo L, Hong X, Liu M, Xiao Y, Zeng X. Shape and Size Dependence of Pharmacokinetics, Biodistribution, and Toxicity of Gold Nanoparticles. Mol Pharm 2025; 22:196-208. [PMID: 39589203 DOI: 10.1021/acs.molpharmaceut.4c00832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2024]
Abstract
Gold nanoparticles (AuNPs) are extensively utilized in biomolecular sensing, photothermal therapy, drug delivery, and various imaging techniques like photoacoustic and fluorescent imaging. Despite their diverse applications, inconsistent findings from previous toxicity studies underscore the critical need for standardized methodologies. This study introduces ten distinct types of AuNPs─cubes, stars, rods, dumbbells, and bipyramids at sizes of 50 and 100 nm, to systematically assess their toxicity under controlled conditions both in vitro and in vivo. Our findings reveal a clear correlation between cytotoxicity and the morphology, size, incubation duration, and concentration of AuNPs. Anisotropically shaped nanoparticles, such as nanorods, nanodumbbells, and nanobipyramids, tend to exhibit higher cytotoxicity compared to more spherical forms like nanocubes and nanostars. Interestingly, while in vivo plasma biochemistry parameters show minimal variation, biodistribution, histopathological alterations, and pharmacokinetics are notably influenced by the shape and size of AuNPs. In most instances, smaller and anisotropic AuNPs that remain in the bloodstream for extended periods are observed. This research offers significant insights into the design of AuNPs with specific morphologies and sizes, particularly for their application in drug delivery systems via intravenous injection. These outcomes emphasize the nuanced toxicity profiles of AuNPs, necessitating tailored approaches in preclinical and clinical research.
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Affiliation(s)
- Huaping Wu
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China
- Department of Cardiology, Clinic Trial Center, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Lin Tang
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China
- Department of Cardiology, Clinic Trial Center, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Huanhuan Dong
- Department of Organic Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China
| | - Maoxin Zhi
- Department of Organic Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China
| | - Liqiong Guo
- Department of Organic Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China
| | - Xuechuan Hong
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China
- Department of Cardiology, Clinic Trial Center, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Mingzhe Liu
- Department of Organic Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China
| | - Yuling Xiao
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China
- Department of Cardiology, Clinic Trial Center, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Xiaodong Zeng
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China
- Department of Cardiology, Clinic Trial Center, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
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Ma X, Poma A. Clinical translation and envisioned impact of nanotech for infection control: Economy, government policy and public awareness. NANOTECHNOLOGY TOOLS FOR INFECTION CONTROL 2025:299-392. [DOI: 10.1016/b978-0-12-823994-0.00004-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Deepak V, El-Balawi L, Harris LK. Placental Drug Delivery to Treat Pre-Eclampsia and Fetal Growth Restriction. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2311165. [PMID: 38745536 DOI: 10.1002/smll.202311165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 04/23/2024] [Indexed: 05/16/2024]
Abstract
Pre-eclampsia and fetal growth restriction (FGR) continue to cause unacceptably high levels of morbidity and mortality, despite significant pharmaceutical and technological advances in other disease areas. The recent pandemic has also impacted obstetric care, as COVID-19 infection increases the risk of poor pregnancy outcomes. This review explores the reasons why it lacks effective drug treatments for the placental dysfunction that underlies many common obstetric conditions and describes how nanomedicines and targeted drug delivery approaches may provide the solution to the current drug drought. The ever-increasing range of biocompatible nanoparticle formulations available is now making it possible to selectively deliver drugs to uterine and placental tissues and dramatically limit fetal drug transfer. Formulations that are refractory to placental uptake offer the possibility of retaining drugs within the maternal circulation, allowing pregnant individuals to take medicines previously considered too harmful to the developing baby. Liposomes, ionizable lipid nanoparticles, polymeric nanoparticles, and adenoviral vectors have all been used to create efficacious drug delivery systems for use in pregnancy, although each approach offers distinct advantages and limitations. It is imperative that recent advances continue to be built upon and that there is an overdue investment of intellectual and financial capital in this field.
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Affiliation(s)
- Venkataraman Deepak
- Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Oxford Road, Manchester, M13 9WL, UK
- St Mary's Hospital, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, M13 9WL, UK
| | - Lujain El-Balawi
- Division of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PL, UK
| | - Lynda K Harris
- Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Oxford Road, Manchester, M13 9WL, UK
- St Mary's Hospital, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, M13 9WL, UK
- Division of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PL, UK
- Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
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Zhao Z, Wu D, Lv D, Zhang X, Chen L, Zhang B. Supported of gold nanoparticles on carboxymethyl lignin modified magnetic nanoparticles as an efficient catalyst for reduction of nitroarenes and treatment of human melanoma. Int J Biol Macromol 2024; 270:132250. [PMID: 38729467 DOI: 10.1016/j.ijbiomac.2024.132250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Revised: 05/05/2024] [Accepted: 05/07/2024] [Indexed: 05/12/2024]
Abstract
This article represents the synthesis and characterizations of Au NPs immobilized and carboxymethyl lignin (CML) modified Fe3O4 nanoparticles (Fe3O4@CML/Au NPs) following a bio-inspired protocol without the participation of any toxic and harmful reductant or stabilizers. Following various physicochemical methodologies, such as FT-IR, FE-SEM, TEM, EDX, XRD, VSM, and ICP-OES, the textural characteristics and different structural aspects were evaluated. The Fe3O4@CML/Au NPs nanocomposite was subsequently explored towards the catalytic reduction of diverse aromatic nitro functions using green conditions. An excellent yield were achieved within very short reaction time. Nine recycling runs of the nanocatalyst were completed without a discernible loss of catalytic activity, thanks to its easy magnetic recovery. The DPPH assay was carried out to examine the antioxidant effectiveness. The Fe3O4@CML/Au NPs nanocomposite inhibited half of the DPPH in a 250 μg/mL solution. To measure the anti-human melanoma efficacy of Fe3O4@CML/Au NPs nanocomposite, MTT assay was applied on HT144, MUM2C, IPC-298 and SKMEL24 cell lines. Fe3O4@CML/Au NPs nanocomposite had high anti-human melanoma efficacy on above tumor cells. The best finding of anti-human melanoma properties of Fe3O4@CML/Au NPs nanocomposite was seen in the case of the SKMEL24 cell line. The IC50 of Fe3O4@CML/Au NPs nanocomposite was 137, 145, 185, and 125 μg/mL against HT144, MUM2C, IPC-298 and SKMEL24 cells, respectively. This research exhibited remarkable anti-human melanoma and antioxidant efficacies of Fe3O4@CML/Au NPs nanocomposite in the in vitro condition.
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Affiliation(s)
- Zunjiang Zhao
- Department of Burns and Plastic Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu 241004, Anhui, China.
| | - Dejin Wu
- Department of Burns and Plastic Surgery, Lu'an People's Hospital, Anhui Medical University, Lu'an 237005, Anhui, China
| | - Dalun Lv
- Department of Burns and Plastic Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu 241004, Anhui, China
| | - Xuan Zhang
- Department of Burns and Plastic Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu 241004, Anhui, China; Department of Burns and Plastic Surgery, An Qing 116 Hospital, An Qing 246003, Anhui, China
| | - Lei Chen
- Department of Burns and Plastic Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu 241004, Anhui, China
| | - Baode Zhang
- Department of Burns and Plastic Surgery, Lu'an People's Hospital, Anhui Medical University, Lu'an 237005, Anhui, China
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Mal S, Chakraborty S, Mahapatra M, Pakeeraiah K, Das S, Paidesetty SK, Roy P. Tackling breast cancer with gold nanoparticles: twinning synthesis and particle engineering with efficacy. NANOSCALE ADVANCES 2024; 6:2766-2812. [PMID: 38817429 PMCID: PMC11134266 DOI: 10.1039/d3na00988b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 04/10/2024] [Indexed: 06/01/2024]
Abstract
The World Health Organization identifies breast cancer as the most prevalent cancer despite predominantly affecting women. Surgery, hormonal therapy, chemotherapy, and radiation therapy are the current treatment modalities. Site-directed nanotherapeutics, engineered with multidimensional functionality are now the frontrunners in breast cancer diagnosis and treatment. Gold nanoparticles with their unique colloidal, optical, quantum, magnetic, mechanical, and electrical properties have become the most valuable weapon in this arsenal. Their advantages include facile modulation of shape and size, a high degree of reproducibility and stability, biocompatibility, and ease of particle engineering to induce multifunctionality. Additionally, the surface plasmon oscillation and high atomic number of gold provide distinct advantages for tailor-made diagnosis, therapy or theranostic applications in breast cancer such as photothermal therapy, radiotherapy, molecular labeling, imaging, and sensing. Although pre-clinical and clinical data are promising for nano-dimensional gold, their clinical translation is hampered by toxicity signs in major organs like the liver, kidneys and spleen. This has instigated global scientific brainstorming to explore feasible particle synthesis and engineering techniques to simultaneously improve the efficacy and versatility and widen the safety window of gold nanoparticles. The present work marks the first study on gold nanoparticle design and maneuvering techniques, elucidating their impact on the pharmacodynamics character and providing a clear-cut scientific roadmap for their fast-track entry into clinical practice.
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Affiliation(s)
- Suvadeep Mal
- Medicinal Chemistry Research Laboratory, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University) Campus-2, Ghatikia, Kalinga Nagar Bhubaneswar Odisha 751003 India
| | | | - Monalisa Mahapatra
- Medicinal Chemistry Research Laboratory, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University) Campus-2, Ghatikia, Kalinga Nagar Bhubaneswar Odisha 751003 India
| | - Kakarla Pakeeraiah
- Medicinal Chemistry Research Laboratory, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University) Campus-2, Ghatikia, Kalinga Nagar Bhubaneswar Odisha 751003 India
| | - Suvadra Das
- Basic Science and Humanities Department, University of Engineering and Management Action Area III, B/5, Newtown Kolkata West Bengal 700160 India
| | - Sudhir Kumar Paidesetty
- Medicinal Chemistry Research Laboratory, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University) Campus-2, Ghatikia, Kalinga Nagar Bhubaneswar Odisha 751003 India
| | - Partha Roy
- GITAM School of Pharmacy, GITAM (Deemed to be University) Vishakhapatnam 530045 India
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Garrigós MM, de Oliveira FA, Costa CJS, Rodrigues LR, Nucci MP, Alves ADH, Mamani JB, Rego GNDA, Munoz JM, Gamarra LF. Assessing the toxicity of one-step-synthesized PEG-coated gold nanoparticles: in vitro and in vivo studies. EINSTEIN-SAO PAULO 2024; 22:eAO0764. [PMID: 38775605 PMCID: PMC11081025 DOI: 10.31744/einstein_journal/2024ao0764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 12/18/2023] [Indexed: 05/25/2024] Open
Abstract
OBJECTIVE To evaluate the in vitro and in vivo toxicities of polyethylene glycol-coated gold nanoparticles synthesized using a one-step process. METHODS Gold nanoparticles were prepared via a co-precipitation method using polyethylene glycol, and the synthesis product was characterized. For the in vitro evaluation, a flow cytometry analysis with Annexin V and iodide propidium staining was used to assess cytotoxicity in MG-63 cells labeled with 10, 50, and 100µg/mL of nanoparticle concentration. For the in vivo evaluation, nanoparticles were administered intraperitoneally at a dose of 10mg/kg dose in 10-week-old mice. Toxicity was assessed 24 hours and 7 days after administration via histopathological analysis of various tissues, as well as through renal, hepatic, and hematopoietic evaluations. RESULTS Synthesized nanoparticles exhibited different hydrodynamic sizes depending on the medium: 51.27±1.62nm in water and 268.12±28.45nm (0 hour) in culture medium. They demonstrated a maximum absorbance at 520nm and a zeta potential of -8.419mV. Cellular viability exceeded 90%, with less than 3% early apoptosis, 6% late apoptosis, and 1% necrosis across all labeling conditions, indicating minimal cytotoxicity differences. Histopathological analysis highlighted the accumulation of nanoparticles in the mesentery; however, no lesions or visible agglomeration was observed in the remaining tissues. Renal, hepatic, and hematopoietic analyses showed no significant differences at any time point. CONCLUSION Polyethylene glycol-coated gold nanoparticles exhibit extremely low toxicity and high biocompatibility, showing promise for future studies.
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Affiliation(s)
- Murilo Montenegro Garrigós
- Hospital Israelita Albert EinsteinSão PauloSPBrazil Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | | | - Cícero Júlio Silva Costa
- Hospital Israelita Albert EinsteinSão PauloSPBrazil Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Lucas Renan Rodrigues
- Hospital Israelita Albert EinsteinSão PauloSPBrazil Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Mariana Penteado Nucci
- Hospital das ClínicasFaculdade MedicinaUniversidade de São PauloSão PauloSPBrazil LIM44 - Hospital das Clínicas, Faculdade Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
| | - Arielly da Hora Alves
- Hospital Israelita Albert EinsteinSão PauloSPBrazil Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Javier Bustamante Mamani
- Hospital Israelita Albert EinsteinSão PauloSPBrazil Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | | | - Juan Matheus Munoz
- Hospital Israelita Albert EinsteinSão PauloSPBrazil Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
| | - Lionel Fernel Gamarra
- Hospital Israelita Albert EinsteinSão PauloSPBrazil Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
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Tapia-Arellano A, Cabrera P, Cortés-Adasme E, Riveros A, Hassan N, Kogan MJ. Tau- and α-synuclein-targeted gold nanoparticles: applications, opportunities, and future outlooks in the diagnosis and therapy of neurodegenerative diseases. J Nanobiotechnology 2024; 22:248. [PMID: 38741193 DOI: 10.1186/s12951-024-02526-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 05/02/2024] [Indexed: 05/16/2024] Open
Abstract
The use of nanomaterials in medicine offers multiple opportunities to address neurodegenerative disorders such as Alzheimer's and Parkinson's disease. These diseases are a significant burden for society and the health system, affecting millions of people worldwide without sensitive and selective diagnostic methodologies or effective treatments to stop their progression. In this sense, the use of gold nanoparticles is a promising tool due to their unique properties at the nanometric level. They can be functionalized with specific molecules to selectively target pathological proteins such as Tau and α-synuclein for Alzheimer's and Parkinson's disease, respectively. Additionally, these proteins are used as diagnostic biomarkers, wherein gold nanoparticles play a key role in enhancing their signal, even at the low concentrations present in biological samples such as blood or cerebrospinal fluid, thus enabling an early and accurate diagnosis. On the other hand, gold nanoparticles act as drug delivery platforms, bringing therapeutic agents directly into the brain, improving treatment efficiency and precision, and reducing side effects in healthy tissues. However, despite the exciting potential of gold nanoparticles, it is crucial to address the challenges and issues associated with their use in the medical field before they can be widely applied in clinical settings. It is critical to ensure the safety and biocompatibility of these nanomaterials in the context of the central nervous system. Therefore, rigorous preclinical and clinical studies are needed to assess the efficacy and feasibility of these strategies in patients. Since there is scarce and sometimes contradictory literature about their use in this context, the main aim of this review is to discuss and analyze the current state-of-the-art of gold nanoparticles in relation to delivery, diagnosis, and therapy for Alzheimer's and Parkinson's disease, as well as recent research about their use in preclinical, clinical, and emerging research areas.
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Affiliation(s)
- Andreas Tapia-Arellano
- Instituto Universitario de Investigación y Desarrollo Tecnológico (IDT), Universidad Tecnológica Metropolitana, Santiago, Chile.
- Facultad de Cs. Qcas. y Farmacéuticas, Universidad de Chile, Santiago, Chile.
- Advanced Center for Chronic Diseases (ACCDis), Santiago, Chile.
- Millenium Nucleus in NanoBioPhysics, Valparaíso, Chile.
| | - Pablo Cabrera
- Facultad de Cs. Qcas. y Farmacéuticas, Universidad de Chile, Santiago, Chile
- Advanced Center for Chronic Diseases (ACCDis), Santiago, Chile
| | - Elizabeth Cortés-Adasme
- Facultad de Cs. Qcas. y Farmacéuticas, Universidad de Chile, Santiago, Chile
- Advanced Center for Chronic Diseases (ACCDis), Santiago, Chile
| | - Ana Riveros
- Facultad de Cs. Qcas. y Farmacéuticas, Universidad de Chile, Santiago, Chile
- Advanced Center for Chronic Diseases (ACCDis), Santiago, Chile
| | - Natalia Hassan
- Instituto Universitario de Investigación y Desarrollo Tecnológico (IDT), Universidad Tecnológica Metropolitana, Santiago, Chile.
- Advanced Center for Chronic Diseases (ACCDis), Santiago, Chile.
- Millenium Nucleus in NanoBioPhysics, Valparaíso, Chile.
| | - Marcelo J Kogan
- Facultad de Cs. Qcas. y Farmacéuticas, Universidad de Chile, Santiago, Chile.
- Advanced Center for Chronic Diseases (ACCDis), Santiago, Chile.
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12
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Jakic K, Selc M, Razga F, Nemethova V, Mazancova P, Havel F, Sramek M, Zarska M, Proska J, Masanova V, Uhnakova I, Makovicky P, Novotova M, Vykoukal V, Babelova A. Long-Term Accumulation, Biological Effects and Toxicity of BSA-Coated Gold Nanoparticles in the Mouse Liver, Spleen, and Kidneys. Int J Nanomedicine 2024; 19:4103-4120. [PMID: 38736658 PMCID: PMC11088863 DOI: 10.2147/ijn.s443168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 04/18/2024] [Indexed: 05/14/2024] Open
Abstract
Introduction Gold nanoparticles are promising candidates as vehicles for drug delivery systems and could be developed into effective anticancer treatments. However, concerns about their safety need to be identified, addressed, and satisfactorily answered. Although gold nanoparticles are considered biocompatible and nontoxic, most of the toxicology evidence originates from in vitro studies, which may not reflect the responses in complex living organisms. Methods We used an animal model to study the long-term effects of 20 nm spherical AuNPs coated with bovine serum albumin. Mice received a 1 mg/kg single intravenous dose of nanoparticles, and the biodistribution and accumulation, as well as the organ changes caused by the nanoparticles, were characterized in the liver, spleen, and kidneys during 120 days. Results The amount of nanoparticles in the organs remained high at 120 days compared with day 1, showing a 39% reduction in the liver, a 53% increase in the spleen, and a 150% increase in the kidneys. The biological effects of chronic nanoparticle exposure were associated with early inflammatory and fibrotic responses in the organs and were more pronounced in the kidneys, despite a negligible amount of nanoparticles found in renal tissues. Conclusion Our data suggest, that although AuNPs belong to the safest nanomaterial platforms nowadays, due to their slow tissue elimination leading to long-term accumulation in the biological systems, they may induce toxic responses in the vital organs, and so understanding of their long-term biological impact is important to consider their potential therapeutic applications.
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Affiliation(s)
- Kristina Jakic
- Department of Nanobiology, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Michal Selc
- Department of Nanobiology, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia
- Centre for Advanced Material Application, Slovak Academy of Sciences, Bratislava, Slovakia
| | | | | | | | - Filip Havel
- Department of Physical Electronics, Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University in Prague, Prague, Czech Republic
- Department of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
| | - Michal Sramek
- Department of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
| | - Monika Zarska
- Department of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
| | - Jan Proska
- Department of Physical Electronics, Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University in Prague, Prague, Czech Republic
| | - Vlasta Masanova
- Department of Metallomics, Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia
| | - Iveta Uhnakova
- Department of Metallomics, Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia
| | - Peter Makovicky
- Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Marta Novotova
- Department of Cellular Cardiology, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Vit Vykoukal
- Department of Chemistry, Faculty of Science, Masaryk University, Brno, Czech Republic
| | - Andrea Babelova
- Department of Nanobiology, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia
- Centre for Advanced Material Application, Slovak Academy of Sciences, Bratislava, Slovakia
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13
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Das SK, Sen K, Ghosh B, Ghosh N, Sinha K, Sil PC. Molecular mechanism of nanomaterials induced liver injury: A review. World J Hepatol 2024; 16:566-600. [PMID: 38689743 PMCID: PMC11056894 DOI: 10.4254/wjh.v16.i4.566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 02/05/2024] [Accepted: 03/19/2024] [Indexed: 04/24/2024] Open
Abstract
The unique physicochemical properties inherent to nanoscale materials have unveiled numerous potential applications, spanning beyond the pharmaceutical and medical sectors into various consumer industries like food and cosmetics. Consequently, humans encounter nanomaterials through diverse exposure routes, giving rise to potential health considerations. Noteworthy among these materials are silica and specific metallic nanoparticles, extensively utilized in consumer products, which have garnered substantial attention due to their propensity to accumulate and induce adverse effects in the liver. This review paper aims to provide an exhaustive examination of the molecular mechanisms underpinning nanomaterial-induced hepatotoxicity, drawing insights from both in vitro and in vivo studies. Primarily, the most frequently observed manifestations of toxicity following the exposure of cells or animal models to various nanomaterials involve the initiation of oxidative stress and inflammation. Additionally, we delve into the existing in vitro models employed for evaluating the hepatotoxic effects of nanomaterials, emphasizing the persistent endeavors to advance and bolster the reliability of these models for nanotoxicology research.
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Affiliation(s)
- Sanjib Kumar Das
- Department of Zoology, Jhargram Raj College, Jhargram 721507, India
| | - Koushik Sen
- Department of Zoology, Jhargram Raj College, Jhargram 721507, India
| | - Biswatosh Ghosh
- Department of Zoology, Bidhannagar College, Kolkata 700064, India
| | - Nabanita Ghosh
- Department of Zoology, Maulana Azad College, Kolkata 700013, India
| | - Krishnendu Sinha
- Department of Zoology, Jhargram Raj College, Jhargram 721507, India.
| | - Parames C Sil
- Department of Molecular Medicine, Bose Institute, Calcutta 700054, India
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14
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Tsuchiya H, Nakamura N, Ohta S. Centrifugal Field-Flow Fractionation Enables Detection of Slight Aggregation of Nanoparticles That Impacts Their Biomedical Applications. Anal Chem 2024; 96:5976-5984. [PMID: 38587278 DOI: 10.1021/acs.analchem.4c00240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/09/2024]
Abstract
Nanoparticles (NPs) are anticipated to be used for various biomedical applications in which their aggregation has been an important issue. However, concerns regarding slightly aggregated but apparently monodispersed NPs have been difficult to address because of a lack of appropriate evaluation methods. Here, we report centrifugal field-flow fractionation (CF3) as a powerful method for analyzing the slight aggregation of NPs, using antibody-modified gold NPs (Ab-AuNPs) prepared by a conventional protocol with centrifugal purification as a model. While common evaluation methods such as dynamic light scattering cannot detect significant signs of aggregation, CF3 successfully detects distinct peaks of slightly aggregated NPs, including dimers and trimers. Their impact on biological interactions was also demonstrated by a cellular uptake study: slightly aggregated Ab-AuNPs exhibited 1.8 times higher cellular uptake than monodispersed Ab-AuNPs. These results suggest the importance of aggregate evaluation via CF3 as well as the need for careful attention to the bioconjugation procedures for NPs.
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Affiliation(s)
- Hiroki Tsuchiya
- Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
| | - Noriko Nakamura
- Institute of Engineering Innovation, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-8656, Japan
- Department of Bioengineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
| | - Seiichi Ohta
- Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
- Institute of Engineering Innovation, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-8656, Japan
- Department of Bioengineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
- Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
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Niżnik Ł, Noga M, Kobylarz D, Frydrych A, Krośniak A, Kapka-Skrzypczak L, Jurowski K. Gold Nanoparticles (AuNPs)-Toxicity, Safety and Green Synthesis: A Critical Review. Int J Mol Sci 2024; 25:4057. [PMID: 38612865 PMCID: PMC11012566 DOI: 10.3390/ijms25074057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 04/03/2024] [Accepted: 04/04/2024] [Indexed: 04/14/2024] Open
Abstract
In recent years, the extensive exploration of Gold Nanoparticles (AuNPs) has captivated the scientific community due to their versatile applications across various industries. With sizes typically ranging from 1 to 100 nm, AuNPs have emerged as promising entities for innovative technologies. This article comprehensively reviews recent advancements in AuNPs research, encompassing synthesis methodologies, diverse applications, and crucial insights into their toxicological profiles. Synthesis techniques for AuNPs span physical, chemical, and biological routes, focusing on eco-friendly "green synthesis" approaches. A critical examination of physical and chemical methods reveals their limitations, including high costs and the potential toxicity associated with using chemicals. Moreover, this article investigates the biosafety implications of AuNPs, shedding light on their potential toxic effects on cellular, tissue, and organ levels. By synthesizing key findings, this review underscores the pressing need for a thorough understanding of AuNPs toxicities, providing essential insights for safety assessment and advancing green toxicology principles.
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Affiliation(s)
- Łukasz Niżnik
- Department of Regulatory and Forensic Toxicology, Institute of Medical Expertise, Łódź, ul. Aleksandrowska 67/93, 91-205 Łódź, Poland (K.J.)
| | - Maciej Noga
- Department of Regulatory and Forensic Toxicology, Institute of Medical Expertise, Łódź, ul. Aleksandrowska 67/93, 91-205 Łódź, Poland (K.J.)
| | - Damian Kobylarz
- Department of Regulatory and Forensic Toxicology, Institute of Medical Expertise, Łódź, ul. Aleksandrowska 67/93, 91-205 Łódź, Poland (K.J.)
| | - Adrian Frydrych
- Laboratory of Innovative Toxicological Research and Analyses, Institute of Medical Studies, Medical College, Rzeszów University, Al. mjr. W. Kopisto 2a, 35-959 Rzeszów, Poland
| | - Alicja Krośniak
- Department of Regulatory and Forensic Toxicology, Institute of Medical Expertise, Łódź, ul. Aleksandrowska 67/93, 91-205 Łódź, Poland (K.J.)
| | - Lucyna Kapka-Skrzypczak
- Department of Molecular Biology and Translational Research, Institute of Rural Health, 20-090 Lublin, Poland
- World Institute for Family Health, Calisia University, 62-800 Kalisz, Poland
| | - Kamil Jurowski
- Department of Regulatory and Forensic Toxicology, Institute of Medical Expertise, Łódź, ul. Aleksandrowska 67/93, 91-205 Łódź, Poland (K.J.)
- Laboratory of Innovative Toxicological Research and Analyses, Institute of Medical Studies, Medical College, Rzeszów University, Al. mjr. W. Kopisto 2a, 35-959 Rzeszów, Poland
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Ghonimi WAM, Abdelrahman FAAF, Salem GA, Dahran N, El sayed SA. The Apoptotic, Oxidative and Histological Changes Induced by Different Diameters of Sphere Gold Nanoparticles (GNPs) with Special Emphasis on the Hepatoprotective Role of Quercetin. Adv Pharm Bull 2024; 14:208-223. [PMID: 38585460 PMCID: PMC10997927 DOI: 10.34172/apb.2024.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 09/24/2023] [Accepted: 10/08/2023] [Indexed: 04/09/2024] Open
Abstract
Purpose Gold nanoparticles (GNPs) as pharmaceutical and drug delivery tools exhibited harmful effects on human health and other living species. Quercetin (Qur) reveals various pharmacological effects specially antioxidant, anti-inflammatory and antiapoptotic. This study is directed to investigate hepatotoxicity of GNPs, in addition, to assess the impact of Qur in mitigating the toxicological effects of GNPs. Methods Groups of rats were treated with or without sphere GNPs (10, 20 and 50 nm) and Qur (200 mg/kg b.wt.). Blood and liver samples from euthanized rats were subjected to biochemical, hematological, histopathological, and immunohistochemical investigations. Results In comparison with 20 and 50 nm treated groups, the 10 nm GNPs significantly increased serum hepatic enzymes, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin. These 10 nm GNPs were associated with oxidative stress and markedly decreased antioxidant enzymes: catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD). Immunohistochemically, 10 nm GNPs expressed intense positive signals in nuclei of hepatocytes when stained with anti-caspase-3 antibody confirming extensive apoptosis. Pre-cotreatment with Qur decreased all tested hepatic enzymes and increased serum level of antioxidant enzymes compared to 10 nm GNPs. Qur treatment strongly exhibited anti-Ki67 antibody (proliferative marker) indicating high proliferation of hepatic parenchyma. Histopathologically, 10 nm GNPs revealed diffuse hydropic degenerations, severe sinusoidal congestion, coagulative necrosis, sever steatosis and diffuse hemosiderosis within the hepatic parenchyma. Qur treatment ameliorated most of these pathological effects. Conclusion The smaller diameters of GNPs induce potential oxidative stress, cytotoxic, and apoptotic effects in hepatic tissues rather than larger ones. In addition, Qur demonstrated a significant prophylactic role against hepatotoxicity of GNPs.
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Affiliation(s)
- Wael A. M. Ghonimi
- Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, 44519 Zagazig, Egypt
| | | | - Gamal A. Salem
- Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, 44519 Zagazig, Egypt
| | - Naief Dahran
- Department of Anatomy, Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia
| | - Shafika A. El sayed
- Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, 44519 Zagazig, Egypt
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ÇAĞLAR M, EŞİTMEZ D, CEBE MS. The Effect of Dose Enhancement in Tumor With Silver Nanoparticles on Surrounding Healthy Tissues: A Monte Carlo Study. Technol Cancer Res Treat 2024; 23:15330338241235771. [PMID: 38449099 PMCID: PMC10919133 DOI: 10.1177/15330338241235771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 01/18/2024] [Accepted: 02/12/2024] [Indexed: 03/08/2024] Open
Abstract
Objectives: Cancer-related death rates account for approximately one-third of all deaths, and this rate is increasing remarkably every year. In this study, we examined the dose enhancement factor (DEF) in the tumor and surrounding tissues by adding different concentrations of silver nanoparticles (AgNPs) to the brain tumor using the Monte Carlo (MC) technique. Methods: This study used MCNP6.2 simulation software. A Planning Target Volume (PTV) of 1 × 1 × 1 cm3 was placed in the center of a cubic cranial model with dimensions of 5 × 5 × 5 cm3. Five different simulations were initially generated using the simple method. These simulations included pure PTV and PTV consisting of 4 different silver concentrations (5, 10, 20, and 30 mg/g). Additionally, a model was created using the nanolattice method, considering the size, position, and distribution of the AgNPs. Irradiation was performed using a source with a 6 MV linac photon spectrum. Measurements were performed using the *f8 tally, and DEF values were calculated. Results: In the simulation study using the simple method, the DEF value of PTV increased linearly with concentration, whereas the DEF values were lower than the simulation results with the nanolattice model (1.9 vs 1.4 for 30 mg/g NP concentration). Performing the simple method, we observed no remarkable dose increase in lateral OARs surrounding PTV. While a remarkable dose decrease was observed in distal OARs, a dose increase in the proximal OAR was observed, which was consistent with that of PTV. However, according to the results obtained by performing the nanolattice method, the dose increase was observed in both the proximal OAR and the distal OAR and was similar to that of PTV. Conclusion: While enhancing the dose in the tumor by adding NPs into the tumor, it is essential to consider whether it also increases the OAR dose. In addition, simulation studies on NPs showed that the dose increase varied significantly with particle size, position, and distribution. Hence, these factors should be considered carefully.
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Affiliation(s)
- Mustafa ÇAĞLAR
- Department of Health Physics, Graduate School of Health Sciences, İstanbul Medipol University, İstanbul, Türkiye
| | - Dursun EŞİTMEZ
- Department of Health Physics, Graduate School of Health Sciences, İstanbul Medipol University, İstanbul, Türkiye
| | - Mehmet Sıddık CEBE
- Department of Health Physics, Graduate School of Health Sciences, İstanbul Medipol University, İstanbul, Türkiye
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18
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Nordin AH, Ngadi N, Nordin ML, Noralidin NA, Nabgan W, Osman AY, Shaari R. Spent tea waste extract as a green modifying agent of chitosan for aspirin adsorption: Fixed-bed column, modeling and toxicity studies. Int J Biol Macromol 2023; 253:126501. [PMID: 37678687 DOI: 10.1016/j.ijbiomac.2023.126501] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 08/12/2023] [Accepted: 08/22/2023] [Indexed: 09/09/2023]
Abstract
Aspirin is a prevalent over-the-counter medicine that has been categorized as an emerging contaminant due to its danger to both living things and the environment. This work presents chitosan modified with spent tea waste extract (STWE) via the wet impregnation method as an adsorbent for the enhanced removal of aspirin in a fixed-bed column. The adsorbent (named chitosan-STWE) was successfully synthesized and exhibited a low crystallinity structure, good stability against thermal and acidic conditions, as depicted by HNMR, XRD, TGA, and the dissolution rate of the adsorbent. The adsorption column study reveals that increasing bed height (up to 6 cm) increases the percentage of aspirin removal (up to 40.8 %). Increasing aspirin concentration enhances the amount of aspirin that comes into contact with the chitosan-STWE adsorbent, thereby increasing the adsorption capacity. On the other hand, higher flow rates result in shorter contact times between the adsorbent and adsorbates, which lowers the quantity of aspirin adsorbed. The experimental data are in accordance with the values generated by the Thomas and Yoon-Nelson models, with the maximum adsorption capacity of 61.7 mg/g. The chitosan-STWE adsorbent was determined to be non-toxic, thus safe to be used in wastewater treatment applications.
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Affiliation(s)
- Abu Hassan Nordin
- Faculty of Chemical and Energy Engineering, Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia; Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM), Arau 02600, Perlis, Malaysia
| | - Norzita Ngadi
- Faculty of Chemical and Energy Engineering, Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia.
| | - Muhammad Luqman Nordin
- Department of Clinical Studies, Faculty of Veterinary Medicine, Universiti Malaysia Kelantan, Pengkalan Chepa, 16100 Kota Bharu, Kelantan, Malaysia
| | - Nur Amalina Noralidin
- Department of Clinical Studies, Faculty of Veterinary Medicine, Universiti Malaysia Kelantan, Pengkalan Chepa, 16100 Kota Bharu, Kelantan, Malaysia
| | - Walid Nabgan
- Departament d'Enginyeria Química, Universitat Rovira I Virgili, Av Països Catalans 26, 43007 Tarragona, Spain
| | - Abdinasir Yusuf Osman
- Department of Pathobiology and Population Science, The Royal Veterinary College, University of London, Hawkshead Lane, North Mymms, Hatfield AL9 7TA, Hertfordshire, UK
| | - Rumaizi Shaari
- Department of Clinical Studies, Faculty of Veterinary Medicine, Universiti Malaysia Kelantan, Pengkalan Chepa, 16100 Kota Bharu, Kelantan, Malaysia
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Abdelhady H, Aleanizy F, Alqahtani F, Bukhari A, Soliman S, Sau S, Iyer A. Visualizing the 4D Impact of Gold Nanoparticles on DNA. Int J Mol Sci 2023; 25:542. [PMID: 38203711 PMCID: PMC10778996 DOI: 10.3390/ijms25010542] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 12/22/2023] [Accepted: 12/28/2023] [Indexed: 01/12/2024] Open
Abstract
The genotoxicity of AuNPs has sparked a scientific debate, with one perspective attributing it to direct DNA damage and another to oxidative damage through reactive oxygen species (ROS) activation. This controversy poses challenges for the widespread use of AuNPs in biomedical applications. To address this debate, we employed four-dimensional atomic force microscopy (4DAFM) to examine the ability of AuNPs to damage DNA in vitro in the absence of ROS. To further examine whether the size and chemical coupling of these AuNPs are properties that control their toxicity, we exposed individual DNA molecules to three different types of AuNPs: small (average diameter = 10 nm), large (average diameter = 22 nm), and large conjugated (average diameter = 39 nm) AuNPs. We found that all types of AuNPs caused rapid (within minutes) and direct damage to the DNA molecules without the involvement of ROS. This research holds significant promise for advancing nanomedicines in diverse areas like viral therapy (including COVID-19), cancer treatment, and biosensor development for detecting DNA damage or mutations by resolving the ongoing debate regarding the genotoxicity mechanism. Moreover, it actively contributes to the continuous endeavors aimed at fully harnessing the capabilities of AuNPs across diverse biomedical fields, promising transformative healthcare solutions.
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Affiliation(s)
- Hosam Abdelhady
- Department of Physiology and Pharmacology, College of Osteopathic Medicine, Sam Houston State University, Conroe, TX 77304, USA
| | - Fadilah Aleanizy
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Fulwah Alqahtani
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Abdullah Bukhari
- College of Medicine, Taibah University, Medina 41477, Saudi Arabia
| | - Sahar Soliman
- Department of Physiology and Pharmacology, College of Osteopathic Medicine, Sam Houston State University, Conroe, TX 77304, USA
| | - Samaresh Sau
- Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy & Health Sciences, Wayne State University, Detroit, MI 48201, USA
| | - Arun Iyer
- Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy & Health Sciences, Wayne State University, Detroit, MI 48201, USA
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Tan KF, In LLA, Vijayaraj Kumar P. Surface Functionalization of Gold Nanoparticles for Targeting the Tumor Microenvironment to Improve Antitumor Efficiency. ACS APPLIED BIO MATERIALS 2023; 6:2944-2981. [PMID: 37435615 DOI: 10.1021/acsabm.3c00202] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/13/2023]
Abstract
Gold nanoparticles (AuNPs) have undergone significant research for their use in the treatment of cancer. Numerous researchers have established their potent antitumor properties, which have greatly impacted the treatment of cancer. AuNPs have been used in four primary anticancer treatment modalities, namely radiation, photothermal therapy, photodynamic therapy, and chemotherapy. However, the ability of AuNPs to destroy cancer is lacking and can even harm healthy cells without the right direction to transport them to the tumor microenvironment. Consequently, a suitable targeting technique is needed. Based on the distinct features of the human tumor microenvironment, this review discusses four different targeting strategies that target the four key features of the tumor microenvironment, including abnormal vasculature, overexpression of specific receptors, an acidic microenvironment, and a hypoxic microenvironment, to direct surface-functionalized AuNPs to the tumor microenvironment and increase antitumor efficacies. In addition, some current completed or ongoing clinical trials of AuNPs will also be discussed below to further reinforce the concept of using AuNPs in anticancer therapy.
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Affiliation(s)
- Kin Fai Tan
- Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, UCSI University, No. 1, Jalan Menara Gading, Taman Connaught, Cheras, Kuala Lumpur 56000, Malaysia
| | - Lionel Lian Aun In
- Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Kuala Lumpur 56000, Malaysia
| | - Palanirajan Vijayaraj Kumar
- Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, UCSI University, No. 1, Jalan Menara Gading, Taman Connaught, Cheras, Kuala Lumpur 56000, Malaysia
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21
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Akkam N, Aljabali AAA, Akkam Y, Abo Alrob O, Al-Trad B, Alzoubi H, Tambuwala MM, Al-Batayneh KM. Investigating the fate and toxicity of green synthesized gold nanoparticles in albino mice. Drug Dev Ind Pharm 2023; 49:508-520. [PMID: 37530565 DOI: 10.1080/03639045.2023.2243334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 07/23/2023] [Accepted: 07/27/2023] [Indexed: 08/03/2023]
Abstract
OBJECTIVE This study aims to investigate the acute and chronic adverse effects of ∼50 nm (nanometer) gold nanoparticles (AuNPs) synthesized using Ziziphus zizyphus leaf extract in mice. SIGNIFICANCE AuNPs have shown promise for medical applications, but their safety and biocompatibility need to be addressed. Understanding the potential adverse effects of AuNPs is crucial to ensure their safe use in medical applications. METHODS The ∼50 nm AuNPs were synthesized using Ziziphus zizyphus leaf extract and characterized using scanning electron microscopy, dynamic light scattering, and zeta potential analysis. Mice were subjected to a single intraperitoneal injection of AuNPs at a dose of 1 g/mg (grams per milligram) or a daily dose of 1 mg/kg for 28 days. Various parameters, including gold bioaccumulation, survival, behavior, body weight, and blood glucose levels, were measured. Histopathological changes and organ indices were assessed. RESULTS Gold levels in the blood and heart did not significantly increase with daily administration of AuNPs. However, there were proportional increases in gold content observed in the liver, spleen, and kidney, indicating effective tissue uptake. Histopathological alterations were predominantly observed in the kidney, suggesting potential tissue injury. CONCLUSIONS The findings of this study indicate that ∼50 nm AuNPs synthesized using Z. zizyphus leaf extract can induce adverse effects, particularly in the kidney, in mice. These results highlight the importance of addressing safety concerns when using AuNPs in medical applications. Further investigations that encompass a comprehensive set of toxicological parameters are necessary to confirm the long-term adverse effects of AuNP exposure.
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Affiliation(s)
- Nosaibah Akkam
- Department of Biological Science, Yarmouk University, Irbid, Jordan
| | - Alaa A A Aljabali
- Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University, Irbid, Jordan
| | - Yazan Akkam
- Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan
| | - Osama Abo Alrob
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan
| | - Bahaa Al-Trad
- Department of Biological Science, Yarmouk University, Irbid, Jordan
| | - Hiba Alzoubi
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Murtaza M Tambuwala
- Lincoln Medical School, University of Lincoln, Brayford Pool Campus, Lincoln, UK
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22
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Roshanbinfar K, Kolesnik‐Gray M, Angeloni M, Schruefer S, Fiedler M, Schubert DW, Ferrazzi F, Krstic V, Engel FB. Collagen Hydrogel Containing Polyethylenimine-Gold Nanoparticles for Drug Release and Enhanced Beating Properties of Engineered Cardiac Tissues. Adv Healthc Mater 2023; 12:e2202408. [PMID: 36976709 PMCID: PMC11468683 DOI: 10.1002/adhm.202202408] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 03/10/2023] [Indexed: 03/29/2023]
Abstract
Cardiac tissue engineering is a promising strategy to prevent heart failure. However, several issues remain unsolved, including efficient electrical coupling and incorporating factors to enhance tissue maturation and vascularization. Herein, a biohybrid hydrogel that enhances beating properties of engineered cardiac tissues and allows drug release concurrently is developed. Gold nanoparticles (AuNPs) with different sizes (18-241 nm) and surface charges (33.9-55.4 mV) are synthesized by reducing gold (III) chloride trihydrate using branched polyethyleneimine (bPEI). These nanoparticles increase gel stiffness from ≈91 to ≈146 kPa, enhance electrical conductivity of collagen hydrogels from ≈40 to 49-68 mS cm-1 , and allow slow and steady release of loaded drugs. Engineered cardiac tissues based on bPEI-AuNP-collagen hydrogels and either primary or human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes show enhanced beating properties. hiPSC-derived cardiomyocytes exhibit more aligned and wider sarcomeres in bPEI-AuNP-collagen hydrogels compared to collagen hydrogels. Furthermore, the presence of bPEI-AuNPs result in advanced electrical coupling evidenced by synchronous and homogenous calcium flux throughout the tissue. RNA-seq analyses are in agreement with these observations. Collectively, this data demonstrate the potential of bPEI-AuNP-collagen hydrogels to improve tissue engineering approaches to prevent heart failure and possibly treat diseases of other electrically sensitive tissues.
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Affiliation(s)
- Kaveh Roshanbinfar
- Experimental Renal and Cardiovascular ResearchDepartment of NephropathologyInstitute of PathologyUniversity of Erlangen‐Nuremberg (FAU)Muscle Research Center Erlangen (MURCE)91054ErlangenGermany
| | - Maria Kolesnik‐Gray
- Department of PhysicsUniversity of Erlangen‐Nuremberg (FAU)Staudtstr. 791058ErlangenGermany
| | - Miriam Angeloni
- Institute of PathologyUniversity of Erlangen‐Nuremberg (FAU)91054ErlangenGermany
| | - Stefan Schruefer
- Institute of Polymer MaterialsDepartment of Materials Science and EngineeringUniversity of Erlangen‐Nuremberg91058ErlangenGermany
| | - Maren Fiedler
- Experimental Renal and Cardiovascular ResearchDepartment of NephropathologyInstitute of PathologyUniversity of Erlangen‐Nuremberg (FAU)Muscle Research Center Erlangen (MURCE)91054ErlangenGermany
| | - Dirk W. Schubert
- Institute of Polymer MaterialsDepartment of Materials Science and EngineeringUniversity of Erlangen‐Nuremberg91058ErlangenGermany
| | - Fulvia Ferrazzi
- Institute of PathologyUniversity of Erlangen‐Nuremberg (FAU)91054ErlangenGermany
- Department of Nephropathology, Institute of Pathology, University of Erlangen‐Nuremberg (FAU)Muscle Research Center Erlangen (MURCE)91054ErlangenGermany
| | - Vojislav Krstic
- Department of PhysicsUniversity of Erlangen‐Nuremberg (FAU)Staudtstr. 791058ErlangenGermany
| | - Felix B. Engel
- Experimental Renal and Cardiovascular ResearchDepartment of NephropathologyInstitute of PathologyUniversity of Erlangen‐Nuremberg (FAU)Muscle Research Center Erlangen (MURCE)91054ErlangenGermany
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23
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Evariste L, Lamas B, Ellero-Simatos S, Khoury L, Cartier C, Gaultier E, Chassaing B, Feltin N, Devoille L, Favre G, Audebert M, Houdeau E. A 90-day oral exposure to food-grade gold at relevant human doses impacts the gut microbiota and the local immune system in a sex-dependent manner in mice. Part Fibre Toxicol 2023; 20:27. [PMID: 37443115 PMCID: PMC10339616 DOI: 10.1186/s12989-023-00539-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 07/06/2023] [Indexed: 07/15/2023] Open
Abstract
BACKGROUND Edible gold (Au) is commonly used as a food additive (E175 in EU) for confectionery and cake decorations, coatings and in beverages. Food-grade gold is most often composed of thin Au sheets or flakes exhibiting micro- and nanometric dimensions in their thickness. Concerns about the impact of mineral particles used as food additives on human health are increasing with respect to the particular physico-chemical properties of nanosized particles, which enable them to cross biological barriers and interact with various body cell compartments. In this study, male and female mice were exposed daily to E175 or an Au nanomaterial (Ref-Au) incorporated into food at relevant human dose for 90 days in order to determine the potential toxicity of edible gold. RESULTS E175 or Ref-Au exposure in mice did not induce any histomorphological damage of the liver, spleen or intestine, nor any genotoxic effects in the colon and liver despite an apparent higher intestinal absorption level of Au particles in mice exposed to Ref-Au compared to the E175 food additive. No changes in the intestinal microbiota were reported after treatment with Ref-Au, regardless of sex. In contrast, after E175 exposure, an increase in the Firmicutes/Bacteroidetes ratio and in the abundance of Proteobacteria were observed in females, while a decrease in the production of short-chain fatty acids occurred in both sexes. Moreover, increased production of IL-6, TNFα and IL-1β was observed in the colon of female mice at the end of the 90-day exposure to E175, whereas, decreased IL-6, IL-1β, IL-17 and TGFβ levels were found in the male colon. CONCLUSIONS These results revealed that a 90-day exposure to E175 added to the diet alters the gut microbiota and intestinal immune response in a sex-dependent manner in mice. Within the dose range of human exposure to E175, these alterations remained low in both sexes and mostly appeared to be nontoxic. However, at the higher dose, the observed gut dysbiosis and the intestinal low-grade inflammation in female mice could favour the occurrence of metabolic disorders supporting the establishment of toxic reference values for the safe use of gold as food additive.
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Affiliation(s)
- Lauris Evariste
- Toxalim UMR1331 (Research Centre in Food Toxicology), Toulouse University, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Bruno Lamas
- Toxalim UMR1331 (Research Centre in Food Toxicology), Toulouse University, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Sandrine Ellero-Simatos
- Toxalim UMR1331 (Research Centre in Food Toxicology), Toulouse University, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France
| | | | - Christel Cartier
- Toxalim UMR1331 (Research Centre in Food Toxicology), Toulouse University, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Eric Gaultier
- Toxalim UMR1331 (Research Centre in Food Toxicology), Toulouse University, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Benoit Chassaing
- INSERM U1016, Team "Mucosal Microbiota in Chronic Inflammatory Diseases", CNRS UMR 8104, Université de Paris, Paris, France
| | | | | | | | - Marc Audebert
- Toxalim UMR1331 (Research Centre in Food Toxicology), Toulouse University, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France
- PrediTox, Toulouse, France
| | - Eric Houdeau
- Toxalim UMR1331 (Research Centre in Food Toxicology), Toulouse University, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France.
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24
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Wen X, Ou L, Cutshaw G, Uthaman S, Ou YC, Zhu T, Szakas S, Carney B, Houghton J, Gundlach-Graham A, Rafat M, Yang K, Bardhan R. Physicochemical Properties and Route of Systemic Delivery Control the In Vivo Dynamics and Breakdown of Radiolabeled Gold Nanostars. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2023; 19:e2204293. [PMID: 36965074 PMCID: PMC10518372 DOI: 10.1002/smll.202204293] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 02/22/2023] [Indexed: 06/18/2023]
Abstract
The in vivo dynamics of nanoparticles requires a mechanistic understanding of multiple factors. Here, for the first time, the surprising breakdown of functionalized gold nanostars (F-AuNSs) conjugated with antibodies and 64 Cu radiolabels in vivo and in artificial lysosomal fluid ex vivo, is shown. The short-term biodistribution of F-AuNSs is driven by the route of systemic delivery (intravenous vs intraperitoneal) and long-term fate is controlled by the tissue type in vivo. In vitro studies including endocytosis pathways, intracellular trafficking, and opsonization, are combined with in vivo studies integrating a milieu of spectroscopy and microcopy techniques that show F-AuNSs dynamics is driven by their physicochemical properties and route of delivery. F-AuNSs break down into sub-20 nm broken nanoparticles as early as 7 days postinjection. Martini coarse-grained simulations are performed to support the in vivo findings. Simulations suggest that shape, size, and charge of the broken nanoparticles, and composition of the lipid membrane depicting various tissues govern the interaction of the nanoparticles with the membrane, and the rate of translocation across the membrane to ultimately enable tissue clearance. The fundamental study addresses critical gaps in the knowledge regarding the fate of nanoparticles in vivo that remain a bottleneck in their clinical translation.
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Affiliation(s)
- Xiaona Wen
- Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, 37235, USA
- Nanovaccine Institute, Iowa State University, Ames, IA, 50012, USA
| | - Luping Ou
- Center for Soft Condensed Matter Physics and Interdisciplinary Research and School of Physical Science and Technology, Soochow University, Suzhou, 215006, China
| | - Gabriel Cutshaw
- Nanovaccine Institute, Iowa State University, Ames, IA, 50012, USA
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, 50012, USA
| | - Saji Uthaman
- Nanovaccine Institute, Iowa State University, Ames, IA, 50012, USA
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, 50012, USA
| | - Yu-Chuan Ou
- Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, 37235, USA
| | - Tian Zhu
- Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, 37235, USA
| | - Sarah Szakas
- Department of Chemistry, Iowa State University, Ames, IA, 50011, USA
| | - Brandon Carney
- Department of Radiology, Stony Brook University, Stony Brook, New York, NY, 11794, USA
| | - Jacob Houghton
- Department of Radiology, Stony Brook University, Stony Brook, New York, NY, 11794, USA
| | | | - Marjan Rafat
- Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, 37235, USA
| | - Kai Yang
- Center for Soft Condensed Matter Physics and Interdisciplinary Research and School of Physical Science and Technology, Soochow University, Suzhou, 215006, China
| | - Rizia Bardhan
- Nanovaccine Institute, Iowa State University, Ames, IA, 50012, USA
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, 50012, USA
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25
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Windell DL, Mourabit S, Moger J, Owen SF, Winter MJ, Tyler CR. The influence of size and surface chemistry on the bioavailability, tissue distribution and toxicity of gold nanoparticles in zebrafish (Danio rerio). ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023; 260:115019. [PMID: 37269610 DOI: 10.1016/j.ecoenv.2023.115019] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 05/05/2023] [Accepted: 05/14/2023] [Indexed: 06/05/2023]
Abstract
Gold nanoparticles (AuNPs) are widely used in biomedicine and their specific properties including, size, geometrics, and surface coating, will affect their fate and behaviour in biological systems. These properties are well studied for their intended biological targets, but there is a lack of understanding on the mechanisms by which AuNPs interact in non-target organisms when they enter the environment. We investigated the effects of size and surface chemistry of AuNPs on their bioavailability, tissue distribution and potential toxicity using zebrafish (Danio rerio) as an experimental model. Larval zebrafish were exposed to fluorescently tagged AuNPs of different sizes (10-100 nm) and surface modifications (TNFα, NHS/PAMAM and PEG), and uptake, tissue distribution and depuration rates were measured using selective-plane illumination microscopy (SPIM). The gut and pronephric tubules were found to contain detectable levels of AuNPs, and the concentration-dependent accumulation was related to the particle size. Surface addition of PEG and TNFα appeared to enhance particle accumulation in the pronephric tubules compared to uncoated particles. Depuration studies showed a gradual removal of particles from the gut and pronephric tubules, although fluorescence indicating the presence of the AuNPs remained in the pronephros 96 h after exposure. Toxicity assessment using two transgenic zebrafish reporter lines, however, revealed no AuNP-related renal injury or cellular oxidative stress. Collectively, our data show that AuNPs used in medical applications across the size range 40-80 nm, are bioavailable to larval zebrafish and some may persist in renal tissue, although their presence did not result in measurable toxicity with respect to pronephric organ function or cellular oxidative stress for short term exposures.
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Affiliation(s)
- Dylan L Windell
- Biosciences, Faculty of Health and Life Sciences, Exeter, Devon EX4 4QD, United Kingdom
| | - Sulayman Mourabit
- Biosciences, Faculty of Health and Life Sciences, Exeter, Devon EX4 4QD, United Kingdom
| | - Julian Moger
- Physics and Medical Imaging, College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, Devon EX4 4QL, United Kingdom
| | - Stewart F Owen
- AstraZeneca, Global Compliance, Alderley Park, Macclesfield, Cheshire SK10 4TF, United Kingdom
| | - Matthew J Winter
- Biosciences, Faculty of Health and Life Sciences, Exeter, Devon EX4 4QD, United Kingdom
| | - Charles R Tyler
- Biosciences, Faculty of Health and Life Sciences, Exeter, Devon EX4 4QD, United Kingdom.
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26
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Ivlieva AL, Petritskaya EN, Rogatkin DA, Zinicovscaia I, Yushin N, Grozdov D. Impact of Chronic Oral Administration of Gold Nanoparticles on Cognitive Abilities of Mice. Int J Mol Sci 2023; 24:ijms24108962. [PMID: 37240304 DOI: 10.3390/ijms24108962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/13/2023] [Accepted: 05/16/2023] [Indexed: 05/28/2023] Open
Abstract
The influence of gold nanoparticles after their prolonged oral administration to mice (during pregnancy and lactation) on spatial memory and anxiety levels in offspring was investigated. Offspring were tested in the Morris water maze and in the elevated Plus-maze. The average specific mass content of gold which crossed the blood-brain barrier was measured using neutron activation analysis and constituted 3.8 ng/g for females and 1.1 ng/g for offspring. Experimental offspring showed no differences in spatial orientation and memory compared to the control, while their anxiety levels increased. Gold nanoparticles influenced the emotional state of mice exposed to nanoparticles during prenatal and early postnatal development, but not their cognitive abilities.
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Affiliation(s)
- Alexandra L Ivlieva
- Institute of Higher Nervous Activity and Neurophysiology of RAS, 5A Butlerova St., 117485 Moscow, Russia
- Moscow Regional Research and Clinical Institute named after M. F. Vladimirsky, Str. Schepkina 61/2, 129110 Moscow, Russia
| | - Elena N Petritskaya
- Institute of Higher Nervous Activity and Neurophysiology of RAS, 5A Butlerova St., 117485 Moscow, Russia
| | - Dmitriy A Rogatkin
- Institute of Higher Nervous Activity and Neurophysiology of RAS, 5A Butlerova St., 117485 Moscow, Russia
| | - Inga Zinicovscaia
- Joint Institute for Nuclear Research, Str. Joliot-Curie 6, 141980 Dubna, Russia
- Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering, 30 Reactorului Str., MG-6, RO-76900 Bucharest-Magurele, Romania
- Institute of Chemistry, Academiei Str. 3, MD-2028 Chisinau, Moldova
| | - Nikita Yushin
- Joint Institute for Nuclear Research, Str. Joliot-Curie 6, 141980 Dubna, Russia
| | - Dmitrii Grozdov
- Joint Institute for Nuclear Research, Str. Joliot-Curie 6, 141980 Dubna, Russia
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27
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Tarantino S, Caricato AP, Rinaldi R, Capomolla C, De Matteis V. Cancer Treatment Using Different Shapes of Gold-Based Nanomaterials in Combination with Conventional Physical Techniques. Pharmaceutics 2023; 15:500. [PMID: 36839822 PMCID: PMC9968101 DOI: 10.3390/pharmaceutics15020500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/23/2023] [Accepted: 01/28/2023] [Indexed: 02/05/2023] Open
Abstract
The conventional methods of cancer treatment and diagnosis, such as radiotherapy, chemotherapy, and computed tomography, have developed a great deal. However, the effectiveness of such methods is limited to the possible failure or collateral effects on the patients. In recent years, nanoscale materials have been studied in the field of medical physics to develop increasingly efficient methods to treat diseases. Gold nanoparticles (AuNPs), thanks to their unique physicochemical and optical properties, were introduced to medicine to promote highly effective treatments. Several studies have confirmed the advantages of AuNPs such as their biocompatibility and the possibility to tune their shapes and sizes or modify their surfaces using different chemical compounds. In this review, the main properties of AuNPs are analyzed, with particular focus on star-shaped AuNPs. In addition, the main methods of tumor treatment and diagnosis involving AuNPs are reviewed.
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Affiliation(s)
- Simona Tarantino
- Department of Mathematics and Physics “E. De Giorgi”, University of Salento, Via Monteroni, 73100 Lecce, Italy
| | - Anna Paola Caricato
- Department of Mathematics and Physics “E. De Giorgi”, University of Salento, Via Monteroni, 73100 Lecce, Italy
- National Institute of Nuclear Physics (INFN), Section of Lecce, Via Monteroni, 73100 Lecce, Italy
| | - Rosaria Rinaldi
- Department of Mathematics and Physics “E. De Giorgi”, University of Salento, Via Monteroni, 73100 Lecce, Italy
| | - Caterina Capomolla
- “Vito Fazzi” Hospital of Lecce, Oncological Center, Piazza Filippo Muratore 1, 73100 Lecce, Italy
| | - Valeria De Matteis
- Department of Mathematics and Physics “E. De Giorgi”, University of Salento, Via Monteroni, 73100 Lecce, Italy
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28
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In Vitro and In Vivo Biological Assays of Dextran Coated Iron Oxide Aqueous Magnetic Fluids. Pharmaceutics 2023; 15:pharmaceutics15010177. [PMID: 36678806 PMCID: PMC9865434 DOI: 10.3390/pharmaceutics15010177] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 12/27/2022] [Accepted: 12/30/2022] [Indexed: 01/05/2023] Open
Abstract
The iron oxide nanoparticles coated with different surface coatings were studied and characterized by multiple physicochemical and biological methods. The present paper aims at estimating the toxicity in vitro and in vivo of dextran coated iron oxide aqueous magnetic fluids. The in vitro studies were conducted by quantifying the viability of HeLa cells after their incubation with the samples (concentrations of 62.5−125−250−500 μg/mL at different time intervals). The estimation of the toxicity in vivo of administering dextran coated iron oxide aqueous magnetic fluids (DIO-AMF) with hydrodynamic diameter of 25.73 ± 4 nm to Male Brown Norway rats has been made. Different concentrations (62.5−125−250−500 μg/mL) of dextran coated iron oxide aqueous magnetic fluids were administered for 7 consecutive days. Hematology and biochemistry of the Male Brown Norway rats assessment was performed at various time intervals (24−72 h and 21−28 days) after intra-peritoneal injection. The results showed that high concentrations of DIO-AMF (250 and 500 μg/mL) significantly increased white blood cells, red blood cells, hemoglobin and hematocrit compared to the values obtained for the control group (p < 0.05). Moreover, following the administration of DIO-AMF, the levels of alkaline phosphatase and aspartate aminotransferase increased compared to the control group (p < 0.05). After DIO-AMF administration, no significant difference was observed in the levels of alanine aminotransferase, gamma-glutamyl transpeptidase, urea and creatinine compared to the control group (p < 0.05). The results of the present study showed that dextran coated iron oxide aqueous magnetic fluids in concentrations lower than 250 μg/mL are reliable for medical and pharmaceutical applications.
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29
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Grebel H, Yu S, Zhang Y. Active carbon based supercapacitors with Au colloids: the case of placing the colloids in close proximity to the electrode interface. NANOSCALE ADVANCES 2022; 5:179-190. [PMID: 36605810 PMCID: PMC9765521 DOI: 10.1039/d2na00794k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 11/11/2022] [Indexed: 06/17/2023]
Abstract
Supercapacitors (SCs) are short-term energy storage elements that find many applications, e.g., electronic charging devices and suppressors of power fluctuations in grids that are interfaced with sustainable sources. The capacitance of an ordinary capacitor increases when dispersing metallic colloids in its dielectric. A similar strategy for SCs means deployment of nano-scale metal colloids (in our case, Au nanoparticles, or AuNPs) at the very narrow interface between an electrolyte and a porous electrode (here, active carbon film, AC, on a grafoil current collector). Unlike previous studies, here we placed AuNPs at a small distance from the electrode. This was achieved by coating the AuNPs with a negatively charged ligand that also enables strong adhesion to the electrode. A very large specific capacitance amplification was demonstrated: for example, C-V data at a scan rate of 20 mV s-1 indicated a specific capacitance amplification of more than 10 when 30 μg of AuNPs was incorporated with 200 mg of active carbon while using a 1 M Na2SO4 electrolyte and a 5% cellulose acetate butyrate binder. Upon replacing the 1 M Na2SO4 electrolyte with 1 M KOH, and keeping the same set of electrodes, the amplification factor decreased but remained large, ∼3, as determined using C-V traces at the same scan rate. This proves that the AuNPs adhered well to the AC electrodes. Simulations indicated the importance of keeping the AuNPs in close proximity to the electrodes, but not in direct contact with them, in order to maintain a substantial amplified polarization effect. Unlike semiconductor embedded electrodes, optical effects were found to be minimal.
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Affiliation(s)
- H Grebel
- Center for Energy Efficiency, Resilience and Innovation (CEERI), The ECE Department at the New Jersey Institute of Technology Newark NJ 07102 USA
| | - Shupei Yu
- Department of Chemistry and Environmental Science at the New Jersey Institute of Technology Newark NJ 07102 USA
| | - Yuanwei Zhang
- Department of Chemistry and Environmental Science at the New Jersey Institute of Technology Newark NJ 07102 USA
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30
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Fakhari S, Jamzad M, Nouri A, Arab-Salmanabadi S, Falaki F. A novel polyamidoamine dendrimer based nano-carrier for oral delivery of imatinib. JOURNAL OF POLYMER RESEARCH 2022. [DOI: 10.1007/s10965-022-03359-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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31
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Lee DG, Lee M, Go EB, Chung N. Resveratrol-loaded gold nanoparticles enhance caspase-mediated apoptosis in PANC-1 pancreatic cells via mitochondrial intrinsic apoptotic pathway. Cancer Nanotechnol 2022. [DOI: 10.1186/s12645-022-00143-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most fatal malignancies. Several chemotherapies employing fluorouracil (5-FU) and gemcitabine were attempted, but the survival rate was extremely low. Resveratrol (RVT), known as a polyphenol compound and phytoalexin, was demonstrated to induce intrinsic apoptosis in cancer cells. However, its low delivery performance and efficiency at tumor sites remain an obstacle to exploit RVT as a drug. To address these problems, we bio-conjugated resveratrol with gold nanoparticles (GNPs) via polyvinylpyrrolidone as a cross-linker (RVT@PVP-GNPs) and investigated whether the fabrications could enhance the delivery performance and anti-tumor efficacy of RVT.
Results
The fabrication of gold nanoparticles (GNPs) and bio-conjugated with resveratrol (RVT@PVP-GNPs) was conducted firstly. TEM image, spectrophotometry and zeta-potential revealed that the GNPs and RVT@PVP-GNPs having a size of approximately 40 nm were successfully synthesized and exhibited moderate stability. GNPs alone represented no damage in PANC-1 cells and moreover diminished the cytotoxicity of RVT in Raw264.7 murine macrophage cells, demonstrating the superiority of gold nanoparticles as a drug carrier. Evaluation using dialysis showed a burst release rate of RVT within 96 h at pH 5.0, demonstrating the possibility of enhanced efficiency of RVT delivery through blood vessels to the tumor. The RVT@PVP-GNPs induced increased rates of S-phase cell cycle arrest and apoptosis compared with free RVT. Notably, RVT@PVP-GNPs diminished the proportion of necrotic cells, whereas free RVT increased it. We also demonstrated that the RVT@PVP-GNPs may induce an apoptosis via intrinsic mitochondria with higher degree compared with free RVT, indicating the possibility of enhanced anti-tumor agents. In animal studies, RVT@PVP-GNPs conjugated with AS1411 aptamer induced efficient tumor volume suppression without accumulation in or damage to the kidneys in vivo.
Conclusions
The results demonstrate that RVT@PVP-GNPs enhance the anti-tumor efficacy of free RVT by activating the intrinsic apoptotic pathway and could be considered as potential anti-tumor drug candidates against pancreatic cancer cells.
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32
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Hočevar S, Puddinu V, Haeni L, Petri-Fink A, Wagner J, Alvarez M, Clift MJD, Bourquin C. PEGylated Gold Nanoparticles Target Age-Associated B Cells In Vivo. ACS NANO 2022; 16:18119-18132. [PMID: 36301574 PMCID: PMC9706664 DOI: 10.1021/acsnano.2c04871] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 10/21/2022] [Indexed: 06/16/2023]
Abstract
Engineered gold nanoparticles (GNPs) have become a useful tool in various therapeutic and diagnostic applications. Uncertainty remains regarding the possible impact of GNPs on the immune system. In this regard, we investigated the interactions of polymer-coated GNPs with B cells and their functions in mice. Surprisingly, we observed that polymer-coated GNPs mainly interact with the recently identified subpopulation of B lymphocytes named age-associated B cells (ABCs). Importantly, we also showed that GNPs did not affect cell viability or the percentages of other B cell populations in different organs. Furthermore, GNPs did not activate B cell innate-like immune responses in any of the tested conditions, nor did they impair adaptive B cell responses in immunized mice. Together, these data provide an important contribution to the otherwise limited knowledge about GNP interference with B cell immune function, and demonstrate that GNPs represent a safe tool to target ABCs in vivo for potential clinical applications.
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Affiliation(s)
- Sandra Hočevar
- Institute
of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva 1211, Switzerland
| | - Viola Puddinu
- Institute
of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva 1211, Switzerland
| | - Laetitia Haeni
- BioNanomaterials,
Adolphe Merkle Institute, University of
Fribourg, Fribourg 1700, Switzerland
| | - Alke Petri-Fink
- BioNanomaterials,
Adolphe Merkle Institute, University of
Fribourg, Fribourg 1700, Switzerland
| | - Julia Wagner
- Institute
of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva 1211, Switzerland
| | - Montserrat Alvarez
- Institute
of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva 1211, Switzerland
| | | | - Carole Bourquin
- Institute
of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva 1211, Switzerland
- Department
of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine,
Faculty of Medicine, University of Geneva, Geneva 1211, Switzerland
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Xulu JH, Ndongwe T, Ezealisiji KM, Tembu VJ, Mncwangi NP, Witika BA, Siwe-Noundou X. The Use of Medicinal Plant-Derived Metallic Nanoparticles in Theranostics. Pharmaceutics 2022; 14:2437. [PMID: 36365255 PMCID: PMC9698412 DOI: 10.3390/pharmaceutics14112437] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/30/2022] [Accepted: 11/01/2022] [Indexed: 08/20/2023] Open
Abstract
In the quest to effectively diagnose and treat the diseases that afflict mankind, the development of a tool capable of simultaneous detection and treatment would provide a significant cornerstone for the survival and control of these diseases. Theranostics denotes a portmanteau of therapeutics and diagnostics which simultaneously detect and treat ailments. Research advances have initiated the advent of theranostics in modern medicine. Overall, theranostics are drug delivery systems with molecular or targeted imaging agents integrated into their structure. The application of theranostics is rising exponentially due to the urgent need for treatments that can be utilized for diagnostic imaging as an aid in precision and personalised medicine. Subsequently, the emergence of nanobiotechnology and the green synthesis of metallic nanoparticles (MNPs) has provided one such avenue for nanoscale development and research. Of interest is the drastic rise in the use of medicinal plants in the synthesis of MNPs which have been reported to be potentially effective in the diagnosis and treatment of diseases. At present, medicinal plant-derived MNPs have been cited to have broad pharmacological applications and have been studied for their potential use in the treatment and management of cancer, malaria, microbial and cardiovascular diseases. The subject of this article regards the role of medicinal plants in the synthesis of MNPs and the potential role of MNPs in the field of theranostics.
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Affiliation(s)
- Jabulile Happiness Xulu
- Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa
| | - Tanaka Ndongwe
- Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa
| | - Kenneth M. Ezealisiji
- Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Port Harcourt, PMB 5323 Choba, Rivers State, Nigeria
| | - Vuyelwa J. Tembu
- Department of Chemistry, Tshwane University of Technology, Pretoria 0001, South Africa
| | - Nontobeko P. Mncwangi
- Department of Pharmacy Practice, School of Pharmacy, Sefako Makgatho Health Sciences University, MEDUNSA, Pretoria 0204, South Africa
| | - Bwalya A. Witika
- Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa
| | - Xavier Siwe-Noundou
- Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa
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Saleh H, Salama M, Hussein RM. Polyethylene glycol capped gold nanoparticles ameliorate renal ischemia-reperfusion injury in diabetic mice through AMPK-Nrf2 signaling pathway. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:77884-77907. [PMID: 35688972 PMCID: PMC9581836 DOI: 10.1007/s11356-022-21235-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 05/29/2022] [Indexed: 05/09/2023]
Abstract
The aim of this study is to investigate the protective effect of polyethylene glycol capped gold nanoparticles (PEG-AuNPs) on renal ischemia-reperfusion injury (I/R)-induced acute kidney injury (AKI) in diabetic mice via the activation of adenosine 5' monophosphate-activated protein kinase-nuclear factor erythroid-2-related factor-2 (AMPK-Nrf2) pathway. Diabetes was induced in male mice (12/group) by streptozotocin (50 mg/kg) for 5 consecutive days. After 4 weeks, the mice have intravenously received doses of PEG-AuNPs (40, 150, and 400 µg/kg body weight) for 3 consecutive days, and then animals were subjected to 30 min ischemia and 48 h reperfusion. Following the treatment with three different doses of PEG-AuNPs, the levels of blood urea nitrogen (BUN) and creatinine were reduced. Obvious reduction in renal tubular atrophy, glomerular damage, mitochondrial damage, and necrotic area were ultra-structurally detected, and renal interstitial inflammation and apoptosis were diminished. Moreover, PEG-AuNPs increased the recovering of damaged renal cells, suppressed significantly levels of malondialdehyde (MDA), downregulated significantly the level of inflammatory cytokines (TNF-α and IL-1β), and upregulated the AMPK-Nrf2 pathway. PEG-AuNPs exhibited a promising alternative therapeutic target for diabetic renal I/R-induced AKI through upregulation of AMPK/PI3K/AKT path which additionally stimulated Nrf2-regulated antioxidant enzymes in a dose-dependent manner.
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Affiliation(s)
- Hanan Saleh
- Department of Zoology, Faculty of Science, Cairo University, P.O. Box 12613, Giza, Egypt
| | - Mohamed Salama
- Textile Research and and Technology Institute, National Research Centre, El Buhouth street Dokki, P.O. Box 12622, Giza, Egypt
| | - Rehab Mohamed Hussein
- Department of Zoology, Faculty of Science, Cairo University, P.O. Box 12613, Giza, Egypt
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Jarrar Q, Al-Doaiss A, Jarrar BM, Alshehri M. On the toxicity of gold nanoparticles: Histological, histochemical and ultrastructural alterations. Toxicol Ind Health 2022; 38:789-800. [PMID: 36253334 DOI: 10.1177/07482337221133881] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Gold nanoparticles (Au NPs) are used in diagnostic and therapeutic applications together with a variety of industrial purposes and in many biomedical sectors with potential risks to human health. The present study aimed to the histological, histochemical, and ultrastructural alterations induced by Au NPS in vital organs. Healthy male Wistar Albino rats (Rattus norvegicus) were subjected to 20 injections of 10-nm Au NPs at a daily dose of 2 mg/kg. Liver, kidney, heart, and lung biopsies from control and Au NPs-treated rats under study were subjected to histological and histochemical examinations. In comparison with the control rats, the renal tissue of Au NPs-treated rats demonstrated glomerular congestion, interstitial inflammatory cell infiltration, renal tubular hydropic degeneration, cloudy swelling, necrosis, and hyaline cast precipitation. In addition, Au NPs induced the following hepatic alterations: hepatocyte cytolysis, cytoplasmic vacuolation, hydropic degeneration, and nuclear alterations together with sinusoidal dilatation. Moreover, the hearts of the treated rats demonstrated myocarditis, cardiac congestion, hyalinosis, cardiomyocyte hydropic degeneration, myofiber disarray and cardiac congestion. The lungs of Au NPs-treated rats also exhibited the following pulmonary alterations: alectasis, emphysema, inflammatory cell inflammation, thickened alveolar walls, pulmonary interstitial edema, congestion, hypersensitivity, fibrocyte proliferation, and honeycombing. In conclusion, exposure to Au NPs induced histological, histochemical and ultrastructural alterations in the vital organs that may alter the function of these organs. Additional efforts are needed for better understanding the potential risks of Au NPs to human health.
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Affiliation(s)
- Qais Jarrar
- Department of Applied Pharmaceutical Sciences and Clinical Pharmacy, Faculty of Pharmacy, 108568Isra University, Amman, Jordan
| | - Amin Al-Doaiss
- Department of Biology, College of Science, 48144King Khalid University, Abha, Saudi Arabia.,Histology Department, College of Medicine, Sana University
| | - Bashir M Jarrar
- Nanobiology Unit, College of Applied Medical Sciences, 123295Jerash University, Jerash, Jordan
| | - Mohammed Alshehri
- Department of Biology, College of Science, 48144King Khalid University, Abha, Saudi Arabia
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36
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Meesaragandla B, Komaragiri Y, Schlüter R, Otto O, Delcea M. The impact of cell culture media on the interaction of biopolymer-functionalized gold nanoparticles with cells: mechanical and toxicological properties. Sci Rep 2022; 12:16643. [PMID: 36198715 PMCID: PMC9534915 DOI: 10.1038/s41598-022-20691-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 09/16/2022] [Indexed: 11/22/2022] Open
Abstract
Understanding the nanoparticle-cell interactions in physiological media is vital in determining the biological fate of the nanoparticles (NPs). These interactions depend on the physicochemical properties of the NPs and their colloidal behavior in cell culture media (CCM). Furthermore, the impact of the bioconjugates made by nanoparticle with proteins from CCM on the mechanical properties of cells upon interaction is unknown. Here, we analyzed the time dependent stability of gold nanoparticles (AuNPs) functionalized with citrate, dextran-10, dextrin and chitosan polymers in protein poor- and protein rich CCM. Further, we implemented the high-throughput technology real-time deformability cytometry (RT-DC) to investigate the impact of AuNP-bioconjugates on the cell mechanics of HL60 suspension cells. We found that dextrin-AuNPs form stable bioconjugates in both CCM and have a little impact on cell mechanics, ROS production and cell viability. In contrast, positively charged chitosan-AuNPs were observed to form spherical and non-spherical aggregated conjugates in both CCM and to induce increased cytotoxicity. Citrate- and dextran-10-AuNPs formed spherical and non-spherical aggregated conjugates in protein rich- and protein poor CCM and induced at short incubation times cell stiffening. We anticipate based on our results that dextrin-AuNPs can be used for therapeutic purposes as they show lower cytotoxicity and insignificant changes in cell physiology.
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Affiliation(s)
- Brahmaiah Meesaragandla
- Biophysical Chemistry, Institute of Biochemistry, University of Greifswald, Felix-Hausdorff-Straße 4, 17489, Greifswald, Germany.,ZIK HIKE-Zentrum Für Innovationskompetenz "Humorale Immunreaktionen Bei Kardiovaskulären Erkrankungen", Fleischmannstraße 42, 17489, Greifswald, Germany
| | - Yesaswini Komaragiri
- ZIK HIKE-Zentrum Für Innovationskompetenz "Humorale Immunreaktionen Bei Kardiovaskulären Erkrankungen", Fleischmannstraße 42, 17489, Greifswald, Germany.,DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung), Partner Site, Greifswald, Germany.,Institute of Physics, University of Greifswald, Felix-Hausdorff-Strasse 6, 17489, Greifswald, Germany
| | - Rabea Schlüter
- Imaging Center of the Department of Biology, University of Greifswald, Friedrich-Ludwig-Jahn-Str. 15, 17489, Greifswald, Germany
| | - Oliver Otto
- ZIK HIKE-Zentrum Für Innovationskompetenz "Humorale Immunreaktionen Bei Kardiovaskulären Erkrankungen", Fleischmannstraße 42, 17489, Greifswald, Germany.,DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung), Partner Site, Greifswald, Germany.,Institute of Physics, University of Greifswald, Felix-Hausdorff-Strasse 6, 17489, Greifswald, Germany
| | - Mihaela Delcea
- Biophysical Chemistry, Institute of Biochemistry, University of Greifswald, Felix-Hausdorff-Straße 4, 17489, Greifswald, Germany. .,ZIK HIKE-Zentrum Für Innovationskompetenz "Humorale Immunreaktionen Bei Kardiovaskulären Erkrankungen", Fleischmannstraße 42, 17489, Greifswald, Germany. .,DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung), Partner Site, Greifswald, Germany.
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Qayyum A, Batool Z, Fatima M, Buzdar SA, Ullah H, Nazir A, Jabeen Q, Siddique S, Imran R. Antibacterial and in vivo toxicological studies of Bi 2O 3/CuO/GO nanocomposite synthesized via cost effective methods. Sci Rep 2022; 12:14287. [PMID: 35995797 PMCID: PMC9395419 DOI: 10.1038/s41598-022-17332-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 07/25/2022] [Indexed: 11/17/2022] Open
Abstract
In this research work, Bi2O3, Bi2O3/GO and Bi2O3/CuO/GO nanocomposites have been synthesized via an eco-friendly green synthesis technique, solgel route and co-precipitation method respectively for the assessment of antibacterial activity as well as in vivo toxicity. The XRD patterns confirm the formation of Bi2O3, Bi2O3/GO and Bi2O3/CuO/GO nanocomposites showing monoclinic structures. Crystallite size and lattice strain are calculated by Scherrer equation, Scherrer plot and Willimson Hall plot methods. Average crystallite size measured for Bi2O3, Bi2O3/GO and Bi2O3/CuO/GO nanocomposites by Scherrer equation, Scherrer plot and WH-plot methods are (5.1, 13.9, 11.5)nm, (5.4, 14.2, 11.3)nm and (5.2, 13.5, 12.0)nm respectively. Optical properties such as absorption peaks and band-gap energies are studied by UV-vis spectroscopy. The FTIR peaks at 513 cm-1, 553 cm-1 and 855 cm-1 confirms the successful synthesis of Bi2O3, Bi2O3/GO and Bi2O3/CuO/GO nanocomposites. The antibacterial activity of synthesized Bi2O3, Bi2O3/GO and Bi2O3/CuO/GO nanocomposites is examined against two gram-negative (Escherichia coli and pseudomonas) as well as gram-positive bacteria (Bacillus cereus and Staphylococcus aureus) at dose 25 mg/kg and 40 mg/kg by disk diffusion technique. Zone of inhibition for Bi2O3, Bi2O3/GO and Bi2O3/CuO/GO at dose 40 mg/kg against E. coli (gram - ve) are 12 mm, 17 mm and 18 mm respectively and against Pseudomonas (gram - ve) are 28 mm, 19 mm and 21 mm respectively. While the zone of inhibition for Bi2O3/GO and Bi2O3/CuO/GO at dose 40 mg/kg against B. cereus (gram + ve) are 8 mm and 8.5 mm respectively and against S. aureus (gram + ve) are 5 mm and 10.5 mm respectively. These amazing results reveal that Bi2O3, Bi2O3/GO and Bi2O3/CuO/GO nanocomposite as a kind of antibacterial content, have enormous potential for biomedical applications. In addition, the in vivo toxicity of synthesized Bi2O3/CuO/GO nanocomposite is investigated on Swiss Albino mice at dose of 20 mg/kg by evaluating immune response, hematology and biochemistry at the time period of 2, 7, 14 and 30 days. No severe damage is observed in mice during whole treatment. The p value calculated by statistical analysis of hematological and biochemistry tests is nonsignificant which ensures that synthesized nanocomposites are safe and non-toxic as they do not affect mice significantly. This study proves that Bi2O3/CuO/GO nanocomposites are biocompatible and can be explored further for different biomedical applications.
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Affiliation(s)
- Asifa Qayyum
- Institute of Physics, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Zahida Batool
- Institute of Physics, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
| | - Mahvish Fatima
- Department of Physics, Deanship of Educational Services, Qassim University, P.O.Box 6595, Buraydah, 51452, Saudi Arabia.
| | - Saeed Ahmad Buzdar
- Institute of Physics, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Hafeez Ullah
- Institute of Physics, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Aalia Nazir
- Institute of Physics, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Qaiser Jabeen
- Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Sofia Siddique
- Department of Physics, University of Engineering and Technology Lahore, Lahore, Pakistan
| | - Rimsha Imran
- Institute of Physics, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
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38
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Adewale OB, Cairncross L, Xakaza H, Wickens N, Anadozie SO, Davids H, Roux S. Short- and long-term effect of colorectal cancer targeting peptides conjugated to gold nanoparticles in rats' liver and colon after single exposure. Toxicol Res 2022; 38:259-273. [PMID: 35874503 PMCID: PMC9247135 DOI: 10.1007/s43188-021-00108-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 09/17/2021] [Accepted: 09/22/2021] [Indexed: 10/20/2022] Open
Abstract
Peptides play important roles in the diagnosis, prognostic predictors, and treatment of various kinds of cancer. Peptides (p.C, p.L and p.14), derived from the phage display peptide libraries, specifically binds to colorectal cancer (CRC) cells in vitro. To allow tumor specificity and selectivity for in vivo diagnosis of CRC, biotinylated p.C, p.L and p.14 were conjugated to AuNPs (14 nm) via the biotin-streptavidin interaction. Male Wistar rats were intravenously injected with a single dose (100 µg/kg body weight) of AuNPs (citrate-AuNPs, PEG-AuNPs, p.C-PEG-, p.L-PEG- and p.14-PEG-AuNPs). Animals were monitored for behavioral changes, and sacrificed either 14 days or 84 days post-injection. Biochemical changes, oxidative stress, and histology of the liver and colon were assessed. No significant changes were noted in the rats injected with all the AuNPs, except p.L-PEG-AuNPs that caused significant toxicity (p < 0.05) 14 days post-exposure when compared to control group, as evidenced by increased relative liver weight, increased malondialdehyde levels and histological changes in the liver. These changes, however, returned to normalcy 84 days post-injection. It can be concluded, based on these findings, that p.L induced a transient toxicity in rats after a single intravenous injection, and can therefore be considered non-toxic long-term after a single exposure.
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Affiliation(s)
- Olusola B. Adewale
- Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth, 6031 South Africa
- Present Address: Department of Chemical Sciences, Biochemistry Program, Afe Babalola University, P.M.B 5454, Ado-Ekiti, Nigeria
| | - Lynn Cairncross
- Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth, 6031 South Africa
| | - Hlumisa Xakaza
- Department of Human Physiology, Nelson Mandela University, Port Elizabeth, 6031 South Africa
| | - Nicolas Wickens
- Department of Medical Laboratory Science, Nelson Mandela University, Port Elizabeth, 6031 South Africa
| | - Scholastica O. Anadozie
- Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth, 6031 South Africa
- Present Address: Department of Chemical Sciences, Biochemistry Program, Afe Babalola University, P.M.B 5454, Ado-Ekiti, Nigeria
| | - Hajierah Davids
- Department of Human Physiology, Nelson Mandela University, Port Elizabeth, 6031 South Africa
| | - Saartjie Roux
- Department of Human Physiology, Nelson Mandela University, Port Elizabeth, 6031 South Africa
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Gray TM, David S, Bassiri N, Patel DY, Kirby N, Mayer KM. Microdosimetric and radiobiological effects of gold nanoparticles at therapeutic radiation energies. Int J Radiat Biol 2022; 99:308-317. [PMID: 35709481 PMCID: PMC10089366 DOI: 10.1080/09553002.2022.2087931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 05/14/2022] [Accepted: 05/30/2022] [Indexed: 02/03/2023]
Abstract
PURPOSE The purpose of this study was to quantify the microscopic dose distribution surrounding gold nanoparticles (GNPs) irradiated at therapeutic energies and to measure the changes in cell survival in vitro caused by this dose enhancement. METHODS The dose distributions from secondary electrons surrounding a single gold nanosphere and single gold nanocube of equal volume were both simulated using MCNP6. Dose enhancement factors (DEFs) in the 1 μm3 volume surrounding a GNP were calculated and compared between a nanosphere and nanocube and between 6 and 18 MV energies. This microscopic effect was explored further by experimentally measuring the cell survival of C-33a cervical cancer cells irradiated at 18 MV with varying doses of energy and concentrations of GNPs. Survival of cells receiving no irradiation, a 3 Gy dose, and a 6 Gy dose of 18 MV energy were determined for each concentration of GNPs. RESULTS It was observed that the dose from electrons surrounding the gold nanocube surpasses that of a gold nanosphere up to a distance of 1.1 μm by 18.5% for the 18 MV energy spectrum and by 23.1% for the 6 MV spectrum. DEFs ranging from ∼2 to 8 were found, with the maximum DEF resulting from the case of the gold nanocube irradiated at 6 MV energy. Experimentally, for irradiation at 18 MV, incubating cells with 6 nM (0.10% gold by mass) GNPs produces an average 6.7% decrease in cell survival, and incubating cells with 9 nM (0.15% gold by mass) GNPs produces an average 14.6% decrease in cell survival, as compared to cells incubated and irradiated without GNPs. CONCLUSION We have successfully demonstrated the potential radiation dose enhancing effects in vitro and microdosimetrically from gold nanoparticles.
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Affiliation(s)
- Tara M Gray
- Department of Physics and Astronomy, The University of Texas at San Antonio, San Antonio, TX, USA
| | - Shaquan David
- Department of Physics and Astronomy, The University of Texas at San Antonio, San Antonio, TX, USA
| | - Nema Bassiri
- Department of Radiation Oncology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
| | | | - Neil Kirby
- Department of Radiation Oncology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
| | - Kathryn M Mayer
- Department of Physics and Astronomy, The University of Texas at San Antonio, San Antonio, TX, USA
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Aguilera-Juárez A, Hernández-Adame L, Ruíz-Gómez MÁ, Monreal-Escalante E, Reyes-Becerril M, Rosales-Mendoza S, Pereyra HGS, Angulo C. LptD-antigen system on gold nanoparticles: an innovative strategy in the nanovaccine development. NANOTECHNOLOGY 2022; 33:295602. [PMID: 35395652 DOI: 10.1088/1361-6528/ac659b] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 04/07/2022] [Indexed: 06/14/2023]
Abstract
Nanovaccine development is a growing research field in which the development of new carriers and bioconjugation approaches is a priority. In this sense, this report describes for the first time, the development of a novel conjugate that consists of gold nanoparticles (AuNPs) obtained by a one-step synthesis using an immunogenic peptide of the Lipopolysaccharide-assembly protein LptD fromVibrio parahaemolyticusbacteria as a reducing and capping agent. The resultingLptD@AuNPscompounds were fully characterized and the results showed the high capacity of the peptide to form complexes and reduce gold ions. The reaction yield estimated was higher than 83% and the chemical integrity of the peptide on the NP surface revealed a tyrosine amino acid bonding on the AuNP surface. Furthermore, theLptD@AuNPsystem showed high colloidal stability in a wide pH range (3-11 pH values), where the hydrodynamic diameter and Zeta potential behavior were strongly influenced by the functional groups of the antigenic peptide. The cytotoxicity assays showed that the obtained system is safe for mouse leukocytes, while immunized mice withLptD@AuNPsproduced specific IgG antibodies. These encouraging results revealed the efficacy of some antigenic peptides as reducers and capping agents, in addition, opening the path to determine immunogenicity and immunoprotective efficacy of theLptD@AuNPsystem against the disease induced byVibrio parahaemolyticus.
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Affiliation(s)
- Ana Aguilera-Juárez
- Immunology & Vaccinology Group. Centro de Investigaciones Biológicas del Noroeste (CIBNOR), Av. Instituto Politécnico Nacional 195, Playa Palo de Santa Rita Sur, La Paz B.C.S. 23096, Mexico
| | - Luis Hernández-Adame
- CONACYT- Centro de Investigaciones Biológicas del Noroeste (CIBNOR), Av. Instituto Politécnico Nacional 195, Playa Palo de Santa Rita Sur, La Paz B.C.S. 23096, Mexico
| | - Miguel Ángel Ruíz-Gómez
- CONACYT-CINVESTAV-IPN Unidad Mérida, Departamento de Física Aplicada, Mérida, Yucatán C.P. 97310, Mexico
| | - Elizabeth Monreal-Escalante
- Immunology & Vaccinology Group. Centro de Investigaciones Biológicas del Noroeste (CIBNOR), Av. Instituto Politécnico Nacional 195, Playa Palo de Santa Rita Sur, La Paz B.C.S. 23096, Mexico
- CONACYT- Centro de Investigaciones Biológicas del Noroeste (CIBNOR), Av. Instituto Politécnico Nacional 195, Playa Palo de Santa Rita Sur, La Paz B.C.S. 23096, Mexico
| | - Martha Reyes-Becerril
- Immunology & Vaccinology Group. Centro de Investigaciones Biológicas del Noroeste (CIBNOR), Av. Instituto Politécnico Nacional 195, Playa Palo de Santa Rita Sur, La Paz B.C.S. 23096, Mexico
| | - Sergio Rosales-Mendoza
- Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr Manuel Nava Núm. 6, Zona Universitaria., San Luis Potosí, S. L. P., C. P. 78210, Mexico
| | - Héctor Gabriel Silva Pereyra
- Instituto Potosino de Investigación Científica y Tecnológica, División de Materiales Avanzados, Camino a la Presa San José 2055, Col. Lomas 4 sección, 78216, San Luis Potosí, SLP, Mexico
| | - Carlos Angulo
- Immunology & Vaccinology Group. Centro de Investigaciones Biológicas del Noroeste (CIBNOR), Av. Instituto Politécnico Nacional 195, Playa Palo de Santa Rita Sur, La Paz B.C.S. 23096, Mexico
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Yang Y, Liu H, Cui L, Liu Y, Fu L, Li B. A Collagen-Derived Oligopeptide from Salmo salar Collagen Hydrolysates Restrains Atherogenesis in ApoE -/- Mice via Targeting P 2 Y 12 Receptor. Mol Nutr Food Res 2022; 66:e2200166. [PMID: 35490399 DOI: 10.1002/mnfr.202200166] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Indexed: 11/06/2022]
Abstract
SCOPE Collagen hydrolysates have been reported with a variety of biological activities. The previous study has separated and identified a series of Hyp-Gly containing antiplatelet peptides from collagen hydrolysates from Salmo salar. But the target and underlying mechanism in platelets remains unknown. METHODS AND RESULTS In this study, peptide OGEFG (OG-5) inhibits platelet aggregation especially induced by 2MeS-ADP and attenuates tail thrombosis formation by 30% in a dose-dependent manner, via apparent antagonism effects on P2 Y12 receptors to regulate Gβγi-PI3K-Akt signaling and Gαi-cAMP-VASP signaling is demonstrated. The molecular docking results also reveal a strong binding energy with the P2 Y12 receptor of peptide OG-5 (-10.70 kcal mol-1 ). In vitro study suggests that OG-5 inhibited the release of inflammatory cytokines in endothelial cells and macrophage cells, migration of vascular smooth muscle cell induced by ADP, which is highly released in ApoE-/- mice. Long-term administration of OG-5 significantly reduces atherosclerotic plaque formation without side effects in ApoE-/- mice, exhibiting a comparable effect with aspirin. CONCLUSION These results reveal that collagen hydrolysates with OG-containing peptides have potential to be developed as an effective diet supplement to prevent the occurrence of atherogenesis and thrombotic disease.
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Affiliation(s)
- Yijie Yang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
| | - Hui Liu
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
| | - Liyuan Cui
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
| | - Yibo Liu
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
| | - Lulu Fu
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
| | - Bo Li
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.,Key Laboratory of Functional Dairy, Ministry of Education, Beijing, 100083, China
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MacCuaig WM, Samykutty A, Foote J, Luo W, Filatenkov A, Li M, Houchen C, Grizzle WE, McNally LR. Toxicity Assessment of Mesoporous Silica Nanoparticles upon Intravenous Injection in Mice: Implications for Drug Delivery. Pharmaceutics 2022; 14:pharmaceutics14050969. [PMID: 35631554 PMCID: PMC9148138 DOI: 10.3390/pharmaceutics14050969] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/26/2022] [Accepted: 04/27/2022] [Indexed: 12/04/2022] Open
Abstract
Nanoparticles are popular tools utilized to selectively deliver drugs and contrast agents for identification and treatment of disease. To determine the usefulness and translational potential of mesoporous silica nanoparticles (MSNs), further evaluations of toxicity are required. MSNs are among the most utilized nano-delivery systems due to ease of synthesis, pore structure, and functionalization. This study aims to elucidate toxicity as a result of intravenous injection of 25 nm MSNs coated with chitosan (C) or polyethylene glycol (PEG) in mice. Following acute and chronic injections, blood was evaluated for standard blood chemistry and complete blood count analyses. Blood chemistry results primarily indicated that no abnormalities were present following acute or chronic injections of MSNs, or C/PEG-coated MSNs. After four weekly administered treatments, vital organs showed minor exacerbation of pre-existing lesions in the 35KPEG-MSN and moderate exacerbation of pre-existing lesions in uncoated MSN and 2KPEG-MSN treatment groups. In contrast, C-MSN treatment groups had minimal changes compared to controls. This study suggests 25 nm MSNs coated with chitosan should elicit minimal toxicity when administered as either single or multiple intravenous injections, but MSNs coated with PEG, especially 2KPEG may exacerbate pre-existing vascular conditions. Further studies should evaluate varying sizes and types of nanoparticles to provide a better overall understanding on the relation between nanoparticles and in vivo toxicity.
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Affiliation(s)
- William M. MacCuaig
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA; (W.M.M.); (A.S.); (W.L.); (A.F.); (M.L.); (C.H.)
- Department of Biomedical Engineering, University of Oklahoma, Norman, OK 73109, USA
| | - Abhilash Samykutty
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA; (W.M.M.); (A.S.); (W.L.); (A.F.); (M.L.); (C.H.)
| | - Jeremy Foote
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;
| | - Wenyi Luo
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA; (W.M.M.); (A.S.); (W.L.); (A.F.); (M.L.); (C.H.)
- Department of Pathology, Oklahoma Health Science Center, Oklahoma City, OK 73104, USA
| | - Alexander Filatenkov
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA; (W.M.M.); (A.S.); (W.L.); (A.F.); (M.L.); (C.H.)
- Department of Pathology, Oklahoma Health Science Center, Oklahoma City, OK 73104, USA
| | - Min Li
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA; (W.M.M.); (A.S.); (W.L.); (A.F.); (M.L.); (C.H.)
- Department of Medicine, Oklahoma Health Science Center, Oklahoma City, OK 73049, USA
| | - Courtney Houchen
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA; (W.M.M.); (A.S.); (W.L.); (A.F.); (M.L.); (C.H.)
- Department of Medicine, Oklahoma Health Science Center, Oklahoma City, OK 73049, USA
| | - William E. Grizzle
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;
| | - Lacey R. McNally
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA; (W.M.M.); (A.S.); (W.L.); (A.F.); (M.L.); (C.H.)
- Department of Surgery, Oklahoma Health Science Center, Oklahoma City, OK 73104, USA
- Correspondence:
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Wang ST, Zhang H, Xuan S, Nykypanchuk D, Zhang Y, Freychet G, Ocko BM, Zuckermann RN, Todorova N, Gang O. Compact Peptoid Molecular Brushes for Nanoparticle Stabilization. J Am Chem Soc 2022; 144:8138-8152. [PMID: 35452210 DOI: 10.1021/jacs.2c00743] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Controlling the interfaces and interactions of colloidal nanoparticles (NPs) via tethered molecular moieties is crucial for NP applications in engineered nanomaterials, optics, catalysis, and nanomedicine. Despite a broad range of molecular types explored, there is a need for a flexible approach to rationally vary the chemistry and structure of these interfacial molecules for controlling NP stability in diverse environments, while maintaining a small size of the NP molecular shell. Here, we demonstrate that low-molecular-weight, bifunctional comb-shaped, and sequence-defined peptoids can effectively stabilize gold NPs (AuNPs). The generality of this robust functionalization strategy was also demonstrated by coating of silver, platinum, and iron oxide NPs with designed peptoids. Each peptoid (PE) is designed with varied arrangements of a multivalent AuNP-binding domain and a solvation domain consisting of oligo-ethylene glycol (EG) branches. Among designs, a peptoid (PE5) with a diblock structure is demonstrated to provide a superior nanocolloidal stability in diverse aqueous solutions while forming a compact shell (∼1.5 nm) on the AuNP surface. We demonstrate by experiments and molecular dynamics simulations that PE5-coated AuNPs (PE5/AuNPs) are stable in select organic solvents owing to the strong PE5 (amine)-Au binding and solubility of the oligo-EG motifs. At the vapor-aqueous interface, we show that PE5/AuNPs remain stable and can self-assemble into ordered 2D lattices. The NP films exhibit strong near-field plasmonic coupling when transferred to solid substrates.
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Affiliation(s)
- Shih-Ting Wang
- Center for Functional Nanomaterials, Brookhaven National Laboratory, Brookhaven Avenue, Upton, New York 11973, United States
| | - Honghu Zhang
- Center for Functional Nanomaterials, Brookhaven National Laboratory, Brookhaven Avenue, Upton, New York 11973, United States
| | - Sunting Xuan
- The Molecular Foundry, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, United States
| | - Dmytro Nykypanchuk
- Center for Functional Nanomaterials, Brookhaven National Laboratory, Brookhaven Avenue, Upton, New York 11973, United States
| | - Yugang Zhang
- Center for Functional Nanomaterials, Brookhaven National Laboratory, Brookhaven Avenue, Upton, New York 11973, United States
| | - Guillaume Freychet
- Energy Sciences Directorate/Photon Science Division, NSLS-II, Brookhaven National Laboratory, Upton, New York 11973, United States
| | - Benjamin M Ocko
- Energy Sciences Directorate/Photon Science Division, NSLS-II, Brookhaven National Laboratory, Upton, New York 11973, United States
| | - Ronald N Zuckermann
- The Molecular Foundry, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, United States
| | - Nevena Todorova
- School of Engineering, RMIT University, GPO Box 2476, Melbourne, Victoria 3001, Australia
| | - Oleg Gang
- Center for Functional Nanomaterials, Brookhaven National Laboratory, Brookhaven Avenue, Upton, New York 11973, United States.,Department of Chemical Engineering, Columbia University, New York, New York 10027, United States.,Department of Applied Physics and Applied Mathematics, Columbia University, New York, New York 10027, United States
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44
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Li X, Zhang Y, Liu G, Luo Z, Zhou L, Xue Y, Liu M. Recent progress in the applications of gold-based nanoparticles towards tumor-targeted imaging and therapy. RSC Adv 2022; 12:7635-7651. [PMID: 35424775 PMCID: PMC8982448 DOI: 10.1039/d2ra00566b] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 03/02/2022] [Indexed: 12/13/2022] Open
Abstract
Cancer death rate remains high all over the world, scientists are paying increasing attention to meet the requirements for precise diagnosis and therapy. Therefore, early diagnosis and active treatment can effectively improve the five-year survival rate of patients. In recent years, gold-based nanomaterials have received increasing attention in medical fields due to their excellent biocompatibility, low toxicity and unique properties. In addition, because of the inherent nature of gold nanomaterials including for computed tomography (CT), fluorescence/optical imaging (FI/OI), surface enhanced Raman spectroscopy imaging (SERS), photoacoustic imaging (PAI) and photothermal therapy (PTT), various gold nanomaterials were developed as theranostic nanoplatforms. In this review, we summarized the latest developments of nanomaterials in imaging and combined therapy, and the prospects for the future application of gold-based theranostic nanoplatforms were also proposed.
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Affiliation(s)
- Xinxin Li
- Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology Wuhan 430205 China
- Institute for Interdisciplinary Research, Jianghan University Wuhan 430056 China
| | - Yiwei Zhang
- Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology Wuhan 430205 China
- Institute for Interdisciplinary Research, Jianghan University Wuhan 430056 China
| | - GuangKuo Liu
- Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology Wuhan 430205 China
- Institute for Interdisciplinary Research, Jianghan University Wuhan 430056 China
| | - Ziyi Luo
- Institute for Interdisciplinary Research, Jianghan University Wuhan 430056 China
| | - Lu Zhou
- Department of Medical Mycology, Shanghai Dermatology Hospital Affiliated to Tongji University Shanghai 200443 China
| | - Yanan Xue
- Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology Wuhan 430205 China
| | - Min Liu
- Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of Education, Jianghan University Wuhan 430056 China
- Institute for Interdisciplinary Research, Jianghan University Wuhan 430056 China
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Influence of Parameters on the Death Pathway of Gastric Cells Induced by Gold Nanosphere Mediated Phototherapy. NANOMATERIALS 2022; 12:nano12040646. [PMID: 35214976 PMCID: PMC8878397 DOI: 10.3390/nano12040646] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/07/2022] [Accepted: 02/13/2022] [Indexed: 02/04/2023]
Abstract
Gold nanosphere (AuS) is a nanosized particle with inert, biocompatible, easily modified surface functionalization and adequate cell penetration ability. Photothermal, photochemical, and vapor effects of AuS could be activated by irradiating with nanosecond laser to cause cell death. Hence, AuS-mediated phototherapy irradiated with nanosecond laser is a promising and minimally-invasive treatment method for cancer therapy. However, various effects require different parameters to be activated. At present, few studies have reported on the influence of parameters of AuS inducing cell death under nanosecond laser irradiation. This makes it very challenging to optimize gold-nanoparticle-mediated specific or synergistic anti-cancer therapy. In this study, we revealed the main parameters and threshold values for AuS-mediated gastric cancer phototherapy with nanosecond pulsed laser irradiation, evaluated the pathway of induced cell death, and discussed the roles of photothermal, photochemical and vapor effects which can induce the cell death. The results showed that AuS-mediated phototherapy activated with nanosecond pulsed laser is an effective method for gastric therapy, mainly based on the photochemical effect. Prolonging the incubation time could decrease the irradiation dose, increase ROS-mediated photothermal effect and vapor effect, and then quickly induce cell death to improve security.
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Zazo H, Colino CI, Gutiérrez-Millán C, Cordero AA, Bartneck M, Lanao JM. Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution. Pharmaceutics 2022; 14:pharmaceutics14020406. [PMID: 35214138 PMCID: PMC8875329 DOI: 10.3390/pharmaceutics14020406] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 02/10/2022] [Accepted: 02/11/2022] [Indexed: 11/16/2022] Open
Abstract
Computational modelling has gained attention for evaluating nanoparticle-based drug delivery systems. Physiologically based pharmacokinetic (PBPK) modelling provides a mechanistic approach for evaluating drug biodistribution. The aim of this work is to develop a specific PBPK model to simulate stavudine biodistribution after the administration of a 40 nm gold nanoparticle-based drug delivery system in rats. The model parameters used have been obtained from literature, in vitro and in vivo studies, and computer optimization. Based on these, the PBPK model was built, and the compartments included were considered as permeability rate-limited tissues. In comparison with stavudine solution, a higher biodistribution of stavudine into HIV reservoirs and the modification of pharmacokinetic parameters such as the mean residence time (MRT) have been observed. These changes are particularly noteworthy in the liver, which presents a higher partition coefficient (from 0.27 to 0.55) and higher MRT (from 1.28 to 5.67 h). Simulated stavudine concentrations successfully describe these changes in the in vivo study results. The average fold error of predicted concentrations after the administration of stavudine-gold nanoparticles was within the 0.5–2-fold error in all of the tissues. Thus, this PBPK model approach may help with the pre-clinical extrapolation to other administration routes or the species of stavudine gold nanoparticles.
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Affiliation(s)
- Hinojal Zazo
- Area of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Avda Lcdo Méndez Nieto, 37007 Salamanca, Spain; (H.Z.); (C.G.-M.); (A.A.C.)
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
| | - Clara I. Colino
- Area of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Avda Lcdo Méndez Nieto, 37007 Salamanca, Spain; (H.Z.); (C.G.-M.); (A.A.C.)
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
- Correspondence: (C.I.C.); (J.M.L.); Tel.: +34-923-294-536 (C.I.C.)
| | - Carmen Gutiérrez-Millán
- Area of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Avda Lcdo Méndez Nieto, 37007 Salamanca, Spain; (H.Z.); (C.G.-M.); (A.A.C.)
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
| | - Andres A. Cordero
- Area of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Avda Lcdo Méndez Nieto, 37007 Salamanca, Spain; (H.Z.); (C.G.-M.); (A.A.C.)
| | - Matthias Bartneck
- Department of Medicine III, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany;
| | - José M. Lanao
- Area of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Avda Lcdo Méndez Nieto, 37007 Salamanca, Spain; (H.Z.); (C.G.-M.); (A.A.C.)
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
- Correspondence: (C.I.C.); (J.M.L.); Tel.: +34-923-294-536 (C.I.C.)
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Liu JJ, Wang Z, Nie LM, Zhu YY, Li G, Lin LL, Chen M, Zhang GJ. RGD-functionalised melanin nanoparticles for intraoperative photoacoustic imaging-guided breast cancer surgery. Eur J Nucl Med Mol Imaging 2022; 49:847-860. [PMID: 34505945 PMCID: PMC8803813 DOI: 10.1007/s00259-021-05545-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 08/24/2021] [Indexed: 02/05/2023]
Abstract
PURPOSE Obtaining tumour-free margins is critical for avoiding re-excision and reducing local recurrence following breast-conserving surgery; however, it remains challenging. Imaging-guided surgery provides precise detection of residual lesions and assists surgical resection. Herein, we described water-soluble melanin nanoparticles (MNPs) conjugated with cyclic Arg-Gly-Asp (cRGD) peptides for breast cancer photoacoustic imaging (PAI) and surgical navigation. METHODS The cRGD-MNPs were synthesised and characterized for morphology, photoacoustic characteristics and stability. Tumour targeting and toxicity of cRGD-MNPs were determined by using either breast cancer cells, MDA-MB-231 tumour-bearing mice or the FVB/N-Tg (MMTV-PyVT) 634Mul/J mice model. PAI was used to locate the tumour and guide surgical resection in MDA-MB-231 tumour-bearing mice. RESULTS The cRGD-MNPs exhibited excellent in vitro and in vivo tumour targeting with low toxicity. Intravenous administration of cRGD-MNPs to MDA-MB-231 tumour-bearing mice showed an approximately 2.1-fold enhancement in photoacoustic (PA) intensity at 2 h, and the ratio of the PA intensity at the tumour site to that in the surrounding normal tissue was 3.2 ± 0.1, which was higher than that using MNPs (1.7 ± 0.3). Similarly, the PA signal in the spontaneous breast cancer increased ~ 2.5-fold at 2 h post-injection of cRGD-MNPs in MMTV-PyVT transgenic mice. Preoperative PAI assessed tumour volume and offered three-dimensional (3D) reconstruction images for accurate surgical planning. Surgical resection following real-time PAI showed high consistency with histopathological analysis. CONCLUSION These results highlight that cRGD-MNP-mediated PAI provide a powerful tool for breast cancer imaging and precise tumour resection. cRGD-MNPs with fine PA properties have great potential for clinical translation.
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Affiliation(s)
- Jing-Jing Liu
- Cancer Center & Department of Breast and Thyroid Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, 2000 Xiang'an Road East, Xiamen, 361101, Fujian, China
- Xiamen Key Laboratory for Endocrine-Related Cancer Precision Medicine, Xiang'an Hospital of Xiamen University, Xiamen, 361101, Fujian, China
| | - Zun Wang
- ChangJiang Scholar's Laboratory, Shantou University Medical College, Shantou, 515041, Guangdong, China
- Department of Breast and Thyroid Surgery, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, 518133, Guangdong, China
| | - Li-Ming Nie
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnosis & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, Fujian, China
- Department of Radiology and Optical Imaging Laboratory, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, China
| | - Yuan-Yuan Zhu
- Cancer Center & Department of Breast and Thyroid Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, 2000 Xiang'an Road East, Xiamen, 361101, Fujian, China
- Xiamen Key Laboratory for Endocrine-Related Cancer Precision Medicine, Xiang'an Hospital of Xiamen University, Xiamen, 361101, Fujian, China
| | - Ge Li
- Cancer Center & Department of Breast and Thyroid Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, 2000 Xiang'an Road East, Xiamen, 361101, Fujian, China
- Xiamen Key Laboratory for Endocrine-Related Cancer Precision Medicine, Xiang'an Hospital of Xiamen University, Xiamen, 361101, Fujian, China
| | - Lin-Ling Lin
- Cancer Center & Department of Breast and Thyroid Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, 2000 Xiang'an Road East, Xiamen, 361101, Fujian, China
- Xiamen Key Laboratory for Endocrine-Related Cancer Precision Medicine, Xiang'an Hospital of Xiamen University, Xiamen, 361101, Fujian, China
| | - Min Chen
- Xiamen Key Laboratory for Endocrine-Related Cancer Precision Medicine, Xiang'an Hospital of Xiamen University, Xiamen, 361101, Fujian, China
- Cancer Research Center, School of Medicine, Xiamen University, Xiamen, 361101, Fujian, China
- Clinical Central Research Core, Xiang'an Hospital of Xiamen University, 2000 Xiang'an Road East, Xiamen, 361101, Fujian, China
| | - Guo-Jun Zhang
- Cancer Center & Department of Breast and Thyroid Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, 2000 Xiang'an Road East, Xiamen, 361101, Fujian, China
- Xiamen Key Laboratory for Endocrine-Related Cancer Precision Medicine, Xiang'an Hospital of Xiamen University, Xiamen, 361101, Fujian, China
- Cancer Research Center, School of Medicine, Xiamen University, Xiamen, 361101, Fujian, China
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Kermanizadeh A, Jacobsen NR, Mroczko A, Brown D, Stone V. Acute hazard assessment of silver nanoparticles following intratracheal instillation, oral and intravenous injection exposures. Nanotoxicology 2022; 15:1295-1311. [PMID: 35015612 DOI: 10.1080/17435390.2021.2020350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
With ever-increasing production and use of nanoparticles (NPs), there is a necessity to evaluate the probability of consequential adverse effects in individuals exposed to these particles. It is now understood that a proportion of NPs can translocate from primary sites of exposure to a range of secondary organs, with the liver, kidneys and spleen being some of the most important. In this study, we carried out a comprehensive toxicological profiling (inflammation, changes in serum biochemistry, oxidative stress, acute phase response and histopathology) of Ag NP induced adverse effects in the three organs of interest following acute exposure of the materials at identical doses via intravenous (IV), intratracheal (IT) instillation and oral administration. The data clearly demonstrated that bioaccumulation and toxicity of the particles were most significant following the IV route of exposure, followed by IT. However, oral exposure to the NPs did not result in any changes that could be interpreted as toxicity in any of the organs of interest within the confines of this investigation. The finding of this study clearly indicates the importance of the route of exposure in secondary organ hazard assessment for NPs. Finally, we identify Connexin 32 (Cx32) as a novel biomarker of NP-mediated hepatic damage which is quantifiable both (in vitro) and in vivo following exposure of physiologically relevant doses.
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Affiliation(s)
- Ali Kermanizadeh
- Human Sciences Research Centre, University of Derby, Derby, United Kingdom
| | - Nicklas R Jacobsen
- National Research Centre for the Working Environment, Copenhagen, Denmark
| | - Agnieszka Mroczko
- Institute of Biological Chemistry, Biophysics and Bioengineering, School of Engineering and Physical Sciences, Heriot Watt University, Edinburgh, United Kingdom
| | - David Brown
- Institute of Biological Chemistry, Biophysics and Bioengineering, School of Engineering and Physical Sciences, Heriot Watt University, Edinburgh, United Kingdom
| | - Vicki Stone
- Institute of Biological Chemistry, Biophysics and Bioengineering, School of Engineering and Physical Sciences, Heriot Watt University, Edinburgh, United Kingdom
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Borova S, Schlutt C, Nickel J, Luxenhofer R. A Transient Initiator for Polypeptoids Postpolymerization
α
‐Functionalization via Activation of a Thioester Group. MACROMOL CHEM PHYS 2022. [DOI: 10.1002/macp.202100331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Solomiia Borova
- Functional Polymer Materials, Chair for Advanced Materials Synthesis, Institute for Functional Materials and Biofabrication, Department of Chemistry and Pharmacy Julius‐Maximilans‐University of Würzburg Röntgenring 11 Würzburg Bavaria 97070 Germany
| | - Christine Schlutt
- Functional Polymer Materials, Chair for Advanced Materials Synthesis, Institute for Functional Materials and Biofabrication, Department of Chemistry and Pharmacy Julius‐Maximilans‐University of Würzburg Röntgenring 11 Würzburg Bavaria 97070 Germany
| | - Joachim Nickel
- Department of Tissue Engineering and Regenerative Medicine University Hospital of Würzburg Röntgenring 11 Würzburg Bavaria 97070 Germany
| | - Robert Luxenhofer
- Functional Polymer Materials, Chair for Advanced Materials Synthesis, Institute for Functional Materials and Biofabrication, Department of Chemistry and Pharmacy Julius‐Maximilans‐University of Würzburg Röntgenring 11 Würzburg Bavaria 97070 Germany
- Soft Matter Chemistry, Department of Chemistry and Helsinki Institute of Sustainability Science, Faculty of Science University of Helsinki P.O. Box 55 Helsinki 00014 Finland
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50
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Bhandari V, Jose S, Badanayak P, Sankaran A, Anandan V. Antimicrobial Finishing of Metals, Metal Oxides, and Metal Composites on Textiles: A Systematic Review. Ind Eng Chem Res 2022. [DOI: 10.1021/acs.iecr.1c04203] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Vandana Bhandari
- Department of Textile and Apparel Designing, I.C. College of Home Science, CCS Haryana Agricultural University, Hisar, India 125004
| | - Seiko Jose
- Textile Manufacturing and Textile Chemistry Division, ICAR- Central Sheep and Wool Research Institute, Avikanagar, Rajasthan, India 304501
| | - Pratikhya Badanayak
- Department of Textile and Apparel Designing, College of Community Science, University of Agricultural Sciences, Dharwad, India 580005
| | - Anuradha Sankaran
- Department of Chemistry, PSNA College of Engineering and Technology, Dindigul, Tamil Nadu India 624622
| | - Vysakh Anandan
- School of Biosciences, Mahatma Gandhi University, Priyadarshini Hills, Kottayam, Kerala India 686560
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