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Song Z, Chen H, Xu W, Zong X, Wang X, Ji Y, Gong J, Pang M, Fung SY, Yang H, Yu Y. The hexapeptide functionalized gold nanoparticles protect against sepsis-associated encephalopathy by forming specific protein corona and regulating macrophage activation. Mater Today Bio 2025; 32:101704. [PMID: 40236814 PMCID: PMC11997411 DOI: 10.1016/j.mtbio.2025.101704] [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: 01/07/2025] [Revised: 03/07/2025] [Accepted: 03/23/2025] [Indexed: 04/17/2025] Open
Abstract
Sepsis-induced systemic inflammatory responses can often lead to brain dysfunction with impaired cognitive function and mobility, known as sepsis-associated encephalopathy (SAE). Currently, there are no effective pharmacological therapeutics to treat SAE. Herein, we demonstrated the hexapeptide functionalized gold nanoparticles P12 that reduced SAE in septic mice with a dual mechanism to down-regulate systemic inflammation. We found that intraperitoneally administered P12 could target macrophages and regulate their inflammatory responses to decrease systemic inflammation and improve mice's cognitive function and mobility with SAE. Depleting peritoneal macrophages diminished the neuroprotective effects of P12 in SAE mice, suggesting macrophages as the effector cells for the neuroprotection by P12. In addition, the proteomic analysis revealed that P12 was capable of sequestering specific circulating inflammatory proteins in the blood of septic mice by forming a protein corona, contributing to the suppression of systemic inflammation. We also found that the local administration of P12 directly to the brain parenchyma effectively inhibited microglia activation and neuroinflammation in mice with SAE. This study provides an insightful understanding of the function and mechanisms of action of P12 in regulating sepsis-associated systemic inflammation and presents a new drug-free nanotherapeutic approach to treat SAE.
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Affiliation(s)
- Zichen Song
- Department of Anesthesia, Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, NO. 154 Anshan Road, Tianjin 300052, China
| | - Hongguang Chen
- Department of Anesthesia, Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, NO. 154 Anshan Road, Tianjin 300052, China
| | - Wenfei Xu
- Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, China
| | - Xiaoye Zong
- Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, China
| | - Xiaoyu Wang
- Department of Immunology and Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, China
| | - Yuting Ji
- Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, China
| | - Jiameng Gong
- Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, China
| | - Mimi Pang
- Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, China
| | - Shan-Yu Fung
- Department of Immunology and Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, China
| | - Hong Yang
- Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, China
| | - Yonghao Yu
- Department of Anesthesia, Tianjin Institute of Anesthesiology, Tianjin Medical University General Hospital, NO. 154 Anshan Road, Tianjin 300052, China
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2
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Razavi ZS, Razavi FS, Alizadeh SS. Inorganic nanoparticles and blood-brain barrier modulation: Advancing targeted neurological therapies. Eur J Med Chem 2025; 287:117357. [PMID: 39947054 DOI: 10.1016/j.ejmech.2025.117357] [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: 12/09/2024] [Revised: 01/19/2025] [Accepted: 01/31/2025] [Indexed: 02/24/2025]
Abstract
The blood-brain barrier (BBB) is a protective barrier that complicates the treatment of neurological disorders. Pharmaceutical compounds encounter significant challenges in crossing the central nervous system (CNS). Nanoparticles (NPs) are promising candidates for treating neurological conditions as they help facilitate drug delivery. This review explores the diverse characteristics and mechanisms of inorganic NPs (INPs), including metal-based, ferric-oxide, and carbon-based nanoparticles, which facilitate their passage through the BBB. Emphasis is placed on the physicochemical properties of NPs such as size, shape, surface charge, and surface modifications and their role in enhancing drug delivery efficacy, reducing immune clearance, and improving BBB permeability. Specific synthesis approaches are demonstrated, with an emphasis on the influence of each one on NP property, biological activity and the capability of an NP for its intended application. As for the advances in the field, the review emphasizes those characterized the NP formulation and surface chemistry that conquered the BBB and tested the need for its alteration. Current findings indicate that NP therapy can in the future enable effective targeting of specific brain disorders and eventually evolve this drug delivery system, which would allow for lower doses with less side effects.
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Affiliation(s)
- Zahra Sadat Razavi
- Physiology Research Center, Iran University Medical Sciences, Tehran, Iran; Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran.
| | - Fateme Sadat Razavi
- Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran
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3
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Carnathan BJ, Stevens D, Shikha S, Slater C, Byford N, Sturdivant RX, Zarzosa K, Braswell WE, Sayes CM. Assessing the Effects of Surface-Stabilized Zero-Valent Iron Nanoparticles on Diverse Bacteria Species Using Complementary Statistical Models. J Funct Biomater 2025; 16:113. [PMID: 40137392 PMCID: PMC11943110 DOI: 10.3390/jfb16030113] [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: 02/20/2025] [Revised: 03/11/2025] [Accepted: 03/14/2025] [Indexed: 03/27/2025] Open
Abstract
Nanoparticles are proposed as alternatives to traditional antimicrobial agents. By manipulating a nanoparticle's core and surface coating, antimicrobial effects against various microbial populations can be customized, known as the "designer effect". However, the antimicrobial properties of nanoparticle core-coating combinations are understudied; little research exists on their effects on diverse bacteria. The antimicrobial effects of surface-stabilized zero-valent iron nanoparticles (FeNPs) are particularly interesting due to their stability in water and ferromagnetic properties. This study explores the impact of FeNPs coated with three surface coatings on six diverse bacterial species. The FeNPs were synthesized and capped with L-ascorbic acid (AA), cetyltrimethylammonium bromide (CTAB), or polyvinylpyrrolidone (PVP) using a bottom-up approach. Zone of inhibition (ZOI) values, assessed through the disc diffusion assay, indicated that AA-FeNPs and CTAB-FeNPs displayed the most potent antibacterial activity. Bacteria inhibition results ranked from most sensitive to least sensitive are the following: Bacillus nealsonii > Escherichia coli > Staphylococcus aureus > Delftia acidovorans > Chryseobacterium sp. > Sphingobacterium multivorum. Comparisons using ordinal regression and generalized linear mixed models revealed significant differences in bacterial responses to the different coatings and nanoparticle concentrations. The statistical model results are in agreement, thus increasing confidence in these conclusions. This study supports the feasibility of the "designer nanoparticle" concept and offers a framework for future research.
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Affiliation(s)
| | - Dinny Stevens
- Department of Environmental Science, Baylor University, Waco, TX 76798, USA; (D.S.)
| | - Swarna Shikha
- Department of Environmental Science, Baylor University, Waco, TX 76798, USA; (D.S.)
| | - Carson Slater
- Department of Statistical Science, Baylor University, Waco, TX 76798, USA (R.X.S.)
| | - Nathen Byford
- Department of Statistical Science, Baylor University, Waco, TX 76798, USA (R.X.S.)
| | - Rodney X. Sturdivant
- Department of Statistical Science, Baylor University, Waco, TX 76798, USA (R.X.S.)
| | - Kuzy Zarzosa
- Department of Environmental Science, Baylor University, Waco, TX 76798, USA; (D.S.)
| | - W. Evan Braswell
- Insect Management and Molecular Diagnostics Laboratory, United States Department of Agriculture, Animal and Plant Health Inspection Service, Plant Protection and Quarantine, Science and Technology, Edinburg, TX 78541, USA;
| | - Christie M. Sayes
- Department of Biology, Baylor University, Waco, TX 76798, USA;
- Department of Environmental Science, Baylor University, Waco, TX 76798, USA; (D.S.)
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4
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Liu Q, Wang M, Dai X, Li S, Guo H, Huang H, Xie Y, Xu C, Liu Y, Tan W. Extreme Tolerance of Nanoparticle-Protein Corona to Ultra-High Abundance Proteins Enhances the Depth of Serum Proteomics. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2413713. [PMID: 39840619 PMCID: PMC11923864 DOI: 10.1002/advs.202413713] [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: 10/26/2024] [Revised: 12/15/2024] [Indexed: 01/23/2025]
Abstract
The serum nanoparticle-protein corona (NPC) provides specific disease information, thus opening a new avenue for high-throughput in-depth proteomics to facilitate biomarker discovery. Yet, little is known about the interactions between NPs and proteins, and its role in enhanced depth of serum proteomics. Herein, a series of protein spike-in experiments are conducted to systematically investigate protein depletion and enrichment during NPC formation. Proteomic depth is serum concentration-dependent, and NPC exhibits powerful tolerance to ultra-high abundant proteins. In addition, protein-protein interactions (PPI), especially those involving albumin, play a pivotal role in promoting proteomic depth. Furthermore, a triple-protein assay is established to interrogate the relationship between protein binding affinity and concentration. NPC formation is a product of balancing binding affinity, concentration, and PPI. Overall, this study elucidates how NPs achieve protein depletion and enrichment for enhanced serum proteomic depth to gain a better understanding of NPC as an essential tool of proteome profiling.
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Affiliation(s)
- Qiqi Liu
- Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM)Chinese Academy of SciencesHangzhouZhejiang310022China
| | - Mengjie Wang
- Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM)Chinese Academy of SciencesHangzhouZhejiang310022China
| | - Xin Dai
- Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM)Chinese Academy of SciencesHangzhouZhejiang310022China
- School of Molecular MedicineHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouZhejiang310024China
| | - Shuangqin Li
- Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM)Chinese Academy of SciencesHangzhouZhejiang310022China
| | - Haoxiang Guo
- Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM)Chinese Academy of SciencesHangzhouZhejiang310022China
| | - Haozhe Huang
- Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM)Chinese Academy of SciencesHangzhouZhejiang310022China
| | - Yueli Xie
- Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM)Chinese Academy of SciencesHangzhouZhejiang310022China
| | - Chenlu Xu
- Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM)Chinese Academy of SciencesHangzhouZhejiang310022China
| | - Yuan Liu
- Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM)Chinese Academy of SciencesHangzhouZhejiang310022China
- School of Molecular MedicineHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouZhejiang310024China
| | - Weihong Tan
- Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM)Chinese Academy of SciencesHangzhouZhejiang310022China
- Institute of Molecular Medicine (IMM)Renji HospitalShanghai Jiao Tong University School of Medicineand College of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityHangzhouShanghai200240China
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5
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Iftode L, Cadinoiu AN, Raţă DM, Atanase LI, Vochiţa G, Rădulescu L, Popa M, Gherghel D. Double Peptide-Functionalized Carboxymethyl Chitosan-Coated Liposomes Loaded with Dexamethasone as a Potential Strategy for Active Targeting Drug Delivery. Int J Mol Sci 2025; 26:922. [PMID: 39940692 PMCID: PMC11816442 DOI: 10.3390/ijms26030922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 01/10/2025] [Accepted: 01/19/2025] [Indexed: 02/16/2025] Open
Abstract
Liposomes are intensively used as nanocarriers for biology, biochemistry, medicine, and in the cosmetics industry and their non-toxic and biocompatible nature makes these vesicles attractive systems for biomedical applications. Moreover, the conjugation of specific ligands to liposomes increases their cellular uptake and therapeutic efficiency. Considering these aspects, the aim of the present study was to obtain new formulations of cationic liposomes coated with dual-peptide functionalized carboxymethyl chitosan (CMCS) for the treatment of inner ear diseases. In order to achieve efficient active targeting and ensuring a high efficacy of the treatment, CMCS was functionalized with Tet1 peptide, to target specific ear cells, and TAT peptide, to ensure cellular penetration. Furthermore, dexamethasone phosphate was loaded as a model drug for the treatment of ear inflammation. The infrared spectroscopy confirmed the functionalization of CMCS with the two specific peptides. The mean diameter of the uncovered liposomes varied between 167 and 198 nm whereas the CMCS-coated liposomes ranged from 179 to 202 nm. TEM analysis showed the spherical shape and unilamellar structure of liposomes. The release efficiency of dexamethasone phosphate after 24 h from the uncoated liposomes was between 37 and 40% and it appeared that the coated liposomes modulated this release. The obtained results demonstrated that the liposomes are hemocompatible since, for a tested concentration of 100 µg/mL, the liposome suspension had a lysis of erythrocytes lower than 2.5% after 180 min of incubation. In addition, the peptide-functionalized CMCS-coated liposomes induced a non-significant effect on the viability of normal V79-4 cells after 48 h, at the highest doses. Values of 71.31% were recorded (CLCP-1), 77.28% (CLCP-2) and 74.36% (CLCP-3), correlated with cytotoxic effects of 28.69%, 22.72%, and 25.64%.
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Affiliation(s)
- Loredana Iftode
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.I.); (L.R.)
- “Cristofor Simionescu” Faculty of Chemical Engineering and Environmental Protection, “Gheorghe Asachi” Technical University, 700050 Iasi, Romania
| | - Anca Niculina Cadinoiu
- Department of Biomaterials, Faculty of Medical Dentistry, “Apollonia” University of Iasi, 700511 Iasi, Romania; (D.M.R.); (L.I.A.)
| | - Delia Mihaela Raţă
- Department of Biomaterials, Faculty of Medical Dentistry, “Apollonia” University of Iasi, 700511 Iasi, Romania; (D.M.R.); (L.I.A.)
| | - Leonard Ionuț Atanase
- Department of Biomaterials, Faculty of Medical Dentistry, “Apollonia” University of Iasi, 700511 Iasi, Romania; (D.M.R.); (L.I.A.)
- Academy of Romanian Scientists, 050044 Bucharest, Romania
| | - Gabriela Vochiţa
- Institute of Biological Research Iasi, Branch of NIRDBS—National Institute of Research and Development of Biological Sciences Bucharest, 700107 Iasi, Romania; (G.V.); (D.G.)
| | - Luminița Rădulescu
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.I.); (L.R.)
| | - Marcel Popa
- “Cristofor Simionescu” Faculty of Chemical Engineering and Environmental Protection, “Gheorghe Asachi” Technical University, 700050 Iasi, Romania
- Department of Biomaterials, Faculty of Medical Dentistry, “Apollonia” University of Iasi, 700511 Iasi, Romania; (D.M.R.); (L.I.A.)
- Academy of Romanian Scientists, 050044 Bucharest, Romania
| | - Daniela Gherghel
- Institute of Biological Research Iasi, Branch of NIRDBS—National Institute of Research and Development of Biological Sciences Bucharest, 700107 Iasi, Romania; (G.V.); (D.G.)
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6
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Talab MJ, Valizadeh A, Tahershamsi Z, Housaindokht MR, Ranjbar B. Personalized biocorona as disease biomarker: The challenges and opportunities. Biochim Biophys Acta Gen Subj 2024; 1868:130724. [PMID: 39426758 DOI: 10.1016/j.bbagen.2024.130724] [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: 06/07/2024] [Revised: 09/22/2024] [Accepted: 10/15/2024] [Indexed: 10/21/2024]
Abstract
It is well known that when nanoparticles interact with biological fluids, a layer of proteins and biological components forms on them. This layer may alter the biological fate and efficiency of the nanomaterial. Recent studies have shown that illness states have a major impact on the structure of the biocorona, sometimes referred to as the "personalized protein corona." Physiological factors like illness, which impact the proteome and metabolome pattern and result in conformational changes in proteins, give rise to this structure of discrimination in biocorona decoration. Improving the efficiency of precise platforms for developing new molecular biomarkers for accurate illness diagnosis is vitally necessary. The biocorona pattern's discrimination may be a diagnostic tool for designing biosensors. As a result, in this review, we summarize the most current studies on the relationship between physiological conditions and the variety of biocorona patterns that influence the biological responses of nanosystems. The biocorona pattern's flexibility may provide new research directions and be utilized to create nanoparticle-based therapeutic and diagnostic products suited to certain physiological situations.
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Affiliation(s)
- Mahtab Jahanshah Talab
- Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ali Valizadeh
- Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Zahra Tahershamsi
- Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mohammad Reza Housaindokht
- Biophysical Chemistry Laboratory, Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
| | - Bijan Ranjbar
- Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
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7
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Hulugalla K, Shofolawe-Bakare OT, Toragall V, Mohammad SA, Mayatt R, Hand K, Anderson J, Chism CM, Misra SK, Shaikh T, Tanner EEL, Smith AE, Sharp J, Fitzkee N, Werfel T. Glycopolymeric Nanoparticles Enrich Less Immunogenic Protein Coronas, Reduce Mononuclear Phagocyte Clearance, and Improve Tumor Delivery Compared to PEGylated Nanoparticles. ACS NANO 2024; 18:30540-30560. [PMID: 39436672 PMCID: PMC12045476 DOI: 10.1021/acsnano.4c08922] [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] [Indexed: 10/23/2024]
Abstract
Nanoparticles (NPs) offer significant promise as drug delivery vehicles; however, their in vivo efficacy is often hindered by the formation of a protein corona (PC), which influences key physiological responses such as blood circulation time, biodistribution, cellular uptake, and intracellular localization. Understanding NP-PC interactions is crucial for optimizing NP design for biomedical applications. Traditional approaches have utilized hydrophilic polymer coatings like polyethylene glycol (PEG) to resist protein adsorption, but glycopolymer-coated nanoparticles have emerged as potential alternatives due to their biocompatibility and ability to reduce the adsorption of highly immunogenic proteins. In this study, we synthesized and characterized glycopolymer-based poly[2-(diisopropylamino)ethyl methacrylate-b-poly(methacrylamidoglucopyranose) (PDPA-b-PMAG) NPs as an alternative to PEGylated NPs. We characterized the polymers using a range of techniques to establish their molecular weight and chemical composition. PMAG and PEG-based NPs showed equivalent physicochemical properties with sizes of ∼100 nm, spherical morphology, and neutral surface charges. We next assessed the magnitude of protein adsorption on both NPs and catalogued the identity of the adsorbed proteins using mass spectrometry-based techniques. The PMAG NPs were found to adsorb fewer proteins in vitro as well as fewer immunogenic proteins such as Immunoglobulins and Complement proteins. Flow cytometry and confocal microscopy were employed to examine cellular uptake in RAW 264.7 macrophages and MDA-MB-231 tumor cells, where PMAG NPs showed higher uptake into tumor cells over macrophages. In vivo studies in BALB/c mice with orthotopic 4T1 breast cancer xenografts showed that PMAG NPs exhibited prolonged circulation times and enhanced tumor accumulation compared to PEGylated NPs. The biodistribution analysis also revealed greater selectivity for tumor tissue over the liver for PMAG NPs. These findings highlight the potential of glycopolymeric NPs to improve tumor targeting and reduce macrophage uptake compared to PEGylated NPs, offering significant advancements in cancer nanomedicine and immunotherapy.
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Affiliation(s)
- Kenneth Hulugalla
- Department of BioMolecular Sciences, University of Mississippi, University, MS, 38677, USA
| | | | - Veeresh Toragall
- Department of Biomedical Engineering, University of Mississippi, University, MS, 38677, USA
| | - Sk Arif Mohammad
- Department of Biomedical Engineering, University of Mississippi, University, MS, 38677, USA
| | - Railey Mayatt
- Department of Chemistry, Mississippi State University, Starkville, MS, USA
| | - Kelsie Hand
- Department of Biomedical Engineering, University of Mississippi, University, MS, 38677, USA
| | - Joshua Anderson
- Department of Biomedical Engineering, University of Mississippi, University, MS, 38677, USA
| | - Claylee M. Chism
- Department of Chemistry and Biochemistry, University of Mississippi, University, MS, USA
| | - Sandeep K. Misra
- Department of BioMolecular Sciences, University of Mississippi, University, MS, 38677, USA
| | - Tanveer Shaikh
- Department of Chemistry, Mississippi State University, Starkville, MS, USA
| | - Eden E. L. Tanner
- Department of Chemistry and Biochemistry, University of Mississippi, University, MS, USA
| | - Adam E. Smith
- Department of Biomedical Engineering, University of Mississippi, University, MS, 38677, USA
- Department of Chemical Engineering, University of Mississippi, University, MS, 38677, USA
| | - Joshua Sharp
- Department of BioMolecular Sciences, University of Mississippi, University, MS, 38677, USA
| | - Nicholas Fitzkee
- Department of Chemistry, Mississippi State University, Starkville, MS, USA
| | - Thomas Werfel
- Department of BioMolecular Sciences, University of Mississippi, University, MS, 38677, USA
- Department of Biomedical Engineering, University of Mississippi, University, MS, 38677, USA
- Department of Chemical Engineering, University of Mississippi, University, MS, 38677, USA
- Cancer Center and Research Institute, University of Mississippi Medical Center, Jackson, MS, 39216, USA
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8
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Rusch R, Chepizhko O, Franosch T. Intermediate scattering function of a gravitactic circle swimmer. Phys Rev E 2024; 110:054606. [PMID: 39690681 DOI: 10.1103/physreve.110.054606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 10/18/2024] [Indexed: 12/19/2024]
Abstract
We analyze gravitaxis of a Brownian circle swimmer by deriving and analytically characterizing the experimentally measurable intermediate scattering function (ISF). To solve the associated Fokker-Planck equation, we use a spectral-theory approach, finding formal expressions in terms of eigenfunctions and eigenvalues of the overdamped-noisy-driven pendulum problem. We further perform a Taylor series of the ISF in the wavevector to extract the cumulants up to the fourth order. We focus on the skewness and kurtosis analyzed for four observation directions in the 2D plane. Validating our findings involves conducting Langevin-dynamics simulations and interpreting the results using a harmonic approximation. The skewness and kurtosis are amplified as the orienting torque approaches the intrinsic angular drift of the circle swimmer from above, highlighting deviations from Gaussian behavior. Transforming the ISF to the comoving frame, a measurable quantity, reveals gravitactic effects and diverse behaviors spanning from diffusive motion at low wavenumbers to circular motion at intermediate wavenumbers and directed motion at higher wavenumbers.
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9
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Zhang Y, Chen Z, Wang X, Yan R, Bao H, Chu X, Guo L, Wang X, Li Y, Mu Y, He Q, Zhang L, Zhang C, Zhou D, Ji D. Site-specific tethering nanobodies on recombinant adeno-associated virus vectors for retargeted gene therapy. Acta Biomater 2024; 187:304-315. [PMID: 39025389 DOI: 10.1016/j.actbio.2024.07.023] [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: 04/01/2024] [Revised: 06/30/2024] [Accepted: 07/11/2024] [Indexed: 07/20/2024]
Abstract
Recombinant adeno-associated viruses (rAAVs) have been extensively studied for decades as carriers for delivering therapeutic genes. However, designing rAAV vectors with selective tropism for specific cell types and tissues has remained challenging. Here, we introduce a strategy for redirecting rAAV by attaching nanobodies with desired tropism at specific sites, effectively replacing the original tropism. To demonstrate this concept, we initially modified the genetic code of rAAV2 to introduce an azido-containing unnatural amino acid at a precise site within the capsid protein. Following a screening process, we identified a critical site (N587+1) where the introduction of unnatural amino acid eliminated the natural tropism of rAAV2. Subsequently, we successfully redirected rAAV2 by conjugating various nanobodies at the N587+1 site, using click and SpyTag-Spycatcher chemistries to form nanobody-AAV conjugates (NACs). By investigating the relationship between NACs quantity and effect and optimizing the linker between rAAV2 and the nanobody using a cathepsin B-susceptible valine-citrulline (VC) dipeptide, we significantly improved gene delivery efficiency both in vitro and in vivo. This enhancement can be attributed to the facilitated endosomal escape of rAAV2. Our method offers an exciting avenue for the rational modification of rAAV2 as a retargeting vehicle, providing a convenient platform for precisely engineering various rAAV2 vectors for both basic research and therapeutic applications. STATEMENT OF SIGNIFICANCE: AAVs hold great promise in the treatment of genetic diseases, but their clinical use has been limited by off-target transduction and efficiency. Here, we report a strategy to construct NACs by conjugating a nanobody or scFv to an rAAV capsid site, specifically via biorthogonal click chemistry and a spy-spycatcher reaction. We explored the structure-effect and quantity-effect relationships of NACs and then optimized the transduction efficiency by introducing a valine-citrulline peptide linker. This approach provides a biocompatible method for rational modification of rAAV as a retargeting platform without structural disruption of the virus or alteration of the binding capacity of the nanobody, with potential utility across a broad spectrum of applications in targeted imaging and gene delivery.
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Affiliation(s)
- Yuanjie Zhang
- Peking University-Yunnan Baiiyao International Medical Research Center, ChemicalBiology Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; Peking University Ningbo Institute of Marine Medicines, Ningbo, China.
| | - Zhiqian Chen
- Peking University-Yunnan Baiiyao International Medical Research Center, ChemicalBiology Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
| | - Xiaoyang Wang
- Peking University-Yunnan Baiiyao International Medical Research Center, ChemicalBiology Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; Peking University Ningbo Institute of Marine Medicines, Ningbo, China.
| | - Rongding Yan
- Peking University-Yunnan Baiiyao International Medical Research Center, ChemicalBiology Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
| | - Han Bao
- Peking University-Yunnan Baiiyao International Medical Research Center, ChemicalBiology Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
| | - Xindang Chu
- Peking University-Yunnan Baiiyao International Medical Research Center, ChemicalBiology Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
| | - Lingfeng Guo
- Peking University-Yunnan Baiiyao International Medical Research Center, ChemicalBiology Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
| | - Xinchen Wang
- Peking University-Yunnan Baiiyao International Medical Research Center, ChemicalBiology Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
| | - Yuanhao Li
- Peking University-Yunnan Baiiyao International Medical Research Center, ChemicalBiology Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; Peking University Ningbo Institute of Marine Medicines, Ningbo, China.
| | - Yu Mu
- Shenzhen Bay Laboratory, Gaoke International Innovation Center, Shenzhen, China.
| | - Qiuchen He
- Peking University-Yunnan Baiiyao International Medical Research Center, ChemicalBiology Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; Peking University Ningbo Institute of Marine Medicines, Ningbo, China.
| | - Lihe Zhang
- Peking University-Yunnan Baiiyao International Medical Research Center, ChemicalBiology Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
| | - Chuanling Zhang
- Peking University-Yunnan Baiiyao International Medical Research Center, ChemicalBiology Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
| | - Demin Zhou
- Peking University-Yunnan Baiiyao International Medical Research Center, ChemicalBiology Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; Shenzhen Bay Laboratory, Gaoke International Innovation Center, Shenzhen, China; Peking University Ningbo Institute of Marine Medicines, Ningbo, China.
| | - Dezhong Ji
- Peking University-Yunnan Baiiyao International Medical Research Center, ChemicalBiology Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; Peking University Ningbo Institute of Marine Medicines, Ningbo, China.
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10
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Imperlini E, Di Marzio L, Cevenini A, Costanzo M, Nicola d'Avanzo, Fresta M, Orrù S, Celia C, Salvatore F. Unraveling the impact of different liposomal formulations on the plasma protein corona composition might give hints on the targeting capability of nanoparticles. NANOSCALE ADVANCES 2024; 6:4434-4449. [PMID: 39170967 PMCID: PMC11334990 DOI: 10.1039/d4na00345d] [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: 04/24/2024] [Accepted: 06/27/2024] [Indexed: 08/23/2024]
Abstract
Nanoparticles (NPs) interact with biological fluids after being injected into the bloodstream. The interactions between NPs and plasma proteins at the nano-bio interface affect their biopharmaceutical properties and distribution in the organ and tissues due to protein corona (PrC) composition, and in turn, modification of the resulting targeting capability. Moreover, lipid and polymer NPs, at their interface, affect the composition of PrC and the relative adsorption and abundance of specific proteins. To investigate this latter aspect, we synthesized and characterized different liposomal formulations (LFs) with lipids and polymer-conjugated lipids at different molar ratios, having different sizes, size distributions and surface charges. The PrC composition of various designed LFs was evaluated ex vivo in human plasma by label-free quantitative proteomics. We also correlated the relative abundance of identified specific proteins in the coronas of the different LFs with their physicochemical properties (size, PDI, zeta potential). The evaluation of outputs from different bioinformatic tools discovered protein clusters allowing to highlight: (i) common as well as the unique species for the various formulations; (ii) correlation between each identified PrC and the physicochemical properties of LFs; (iii) some preferential binding determined by physicochemical properties of LFs; (iv) occurrence of formulation-specific protein patterns in PrC. Investigating specific clusters in PrC will help decode the multivalent roles of the protein pattern components in the drug delivery process, taking advantage of the bio-nanoscale recognition and identification for significant advances in nanomedicine.
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Affiliation(s)
- Esther Imperlini
- Department for Innovation in Biological, Agrofood and Forest Systems, University of Tuscia Viterbo 01100 Italy
| | - Luisa Di Marzio
- Department of Pharmacy, University of Chieti - Pescara "G. d'Annunzio" Via dei Vestini 31 66100 Chieti Italy +39 0871 3554711
| | - Armando Cevenini
- Department of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II Naples 80131 Italy +39 3356069177
- CEINGE-Biotecnologie Avanzate Franco Salvatore Naples 80145 Italy +39 081 3737880
| | - Michele Costanzo
- Department of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II Naples 80131 Italy +39 3356069177
- CEINGE-Biotecnologie Avanzate Franco Salvatore Naples 80145 Italy +39 081 3737880
| | - Nicola d'Avanzo
- Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia" Viale "S. Venuta" 88100 Catanzaro Italy
- Department of Experimental and Clinical Medicine, Research Center "ProHealth Translational Hub", "Magna Graecia" University of Catanzaro, Campus Universitario "S. Venuta"-Building of BioSciences Viale S. Venuta 88100 Catanzaro Italy
| | - Massimo Fresta
- Department of Experimental and Clinical Medicine, Research Center "ProHealth Translational Hub", "Magna Graecia" University of Catanzaro, Campus Universitario "S. Venuta"-Building of BioSciences Viale S. Venuta 88100 Catanzaro Italy
- Department of Health Sciences, University of Catanzaro "Magna Graecia" Viale "S. Venuta" 88100 Catanzaro Italy
| | - Stefania Orrù
- CEINGE-Biotecnologie Avanzate Franco Salvatore Naples 80145 Italy +39 081 3737880
- Department of Medical, Movement and Wellness Sciences, University of Naples Parthenope Naples 80133 Italy
| | - Christian Celia
- Department of Pharmacy, University of Chieti - Pescara "G. d'Annunzio" Via dei Vestini 31 66100 Chieti Italy +39 0871 3554711
- Lithuanian University of Health Sciences, Laboratory of Drug Targets Histopathology, Institute of Cardiology A. Mickeviciaus g. 9 LT-44307 Kaunas Lithuania
- Institute of Nanochemistry and Nanobiology, School of Environmental and Chemical Engineering, Shanghai University Shanghai 200444 China
- UdA-TechLab, Research Center, University of Chieti-Pescara "G. D'Annunzio" 66100 Chieti Italy
| | - Francesco Salvatore
- Department of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples Federico II Naples 80131 Italy +39 3356069177
- CEINGE-Biotecnologie Avanzate Franco Salvatore Naples 80145 Italy +39 081 3737880
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11
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Ghosh R, Roy L, Mukherjee D, Sarker S, Mondal J, Pan N, Hasan MN, Ghosh S, Chattopadhyay A, Adhikary A, Bhattacharyya M, Mallick AK, Biswas R, Das R, Pal SK. Structurally Dynamic Monocyte-Liposome Hybrid Vesicles as an Anticancer Drug Delivery Vehicle: A Crucial Correlation of Microscopic Elasticity and Ultrafast Dynamics. J Phys Chem Lett 2024; 15:3078-3088. [PMID: 38467015 DOI: 10.1021/acs.jpclett.3c03192] [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: 03/13/2024]
Abstract
A biomimetic cell-based carrier system based on monocyte membranes and liposomes has been designed to create a hybrid "Monocyte-LP" which inherits the surface antigens of the monocytes along with the drug encapsulation property of the liposome. Förster resonance energy transfer (FRET) and polarization gated anisotropy measurements show the stiffness of the vesicles obtained from monocyte membranes (Mons), phosphatidylcholine membranes (LP), and Monocyte-LP to follow an increasing order of Mons > Monocyte-LP > LP. The dynamics of interface bound water molecules plays a key role in the elasticity of the vesicles, which in turn imparts higher delivery efficacy to the hybrid Monocyte-LP for a model anticancer drug doxorubicin than the other two vesicles, indicating a critical balance between flexibility and rigidity for an efficient cellular uptake. The present work provides insight on the influence of elasticity of delivery vehicles for enhanced drug delivery.
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Affiliation(s)
- Ria Ghosh
- Department of Biochemistry, University of Calcutta 35 Ballygunge Circular Road, Ballygunge, Kolkata 700019, India
- Department of Chemical and Biological Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III, Salt Lake, Kolkata 700106, India
| | - Lopamudra Roy
- Department of Applied Optics and Photonics, University of Calcutta, Block-JD, Sector-III, Saltlake, Kolkata 700106, India
| | - Dipanjan Mukherjee
- Department of Chemical and Biological Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III, Salt Lake, Kolkata 700106, India
| | - Sushmita Sarker
- Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, Salt Lake, Kolkata 700106, India
| | - Jayanta Mondal
- Department of Chemical and Biological Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III, Salt Lake, Kolkata 700106, India
| | - Nivedita Pan
- Department of Chemical and Biological Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III, Salt Lake, Kolkata 700106, India
| | - Md Nur Hasan
- Department of Chemical and Biological Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III, Salt Lake, Kolkata 700106, India
| | - Subhajit Ghosh
- Department of Life Science & Biotechnology, Jadavpur University, 188, Raja Subodh Chandra Mallick Rd, Jadavpur, Kolkata, West Bengal 700032, India
| | - Arpita Chattopadhyay
- Department of Basic science and Humanities, Techno International New Town Block, DG 1/1, Action Area 1, New Town, Rajarhat, Kolkata 700156, India
| | - Arghya Adhikary
- Department of Life Science & Biotechnology, Jadavpur University, 188, Raja Subodh Chandra Mallick Rd, Jadavpur, Kolkata, West Bengal 700032, India
| | - Maitree Bhattacharyya
- Department of Biochemistry, University of Calcutta 35 Ballygunge Circular Road, Ballygunge, Kolkata 700019, India
| | - Asim Kumar Mallick
- Department of Paediatric Medicine, Nil RatanSircar Medical College & Hospital, 138, AJC Bose Road, Sealdah, Raja Bazar, Kolkata 700014, India
| | - Ranjit Biswas
- Department of Chemical and Biological Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III, Salt Lake, Kolkata 700106, India
| | - Ranjan Das
- Department of Chemistry, West Bengal State University, Barasat, Kolkata 700126, India
| | - Samir Kumar Pal
- Department of Chemical and Biological Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III, Salt Lake, Kolkata 700106, India
- Technical Research Centre, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III, Salt Lake, Kolkata, West Bengal 700106, India
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12
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Bisht T, Adhikari A, Patil S, Dhoundiyal S. Bioconjugation Techniques for Enhancing Stability and Targeting Efficiency of Protein and Peptide Therapeutics. Curr Protein Pept Sci 2024; 25:226-243. [PMID: 37921168 DOI: 10.2174/0113892037268777231013154850] [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: 06/23/2023] [Revised: 09/05/2023] [Accepted: 09/15/2023] [Indexed: 11/04/2023]
Abstract
Bioconjugation techniques have emerged as powerful tools for enhancing the stability and targeting efficiency of protein and peptide therapeutics. This review provides a comprehensive analysis of the various bioconjugation strategies employed in the field. The introduction highlights the significance of bioconjugation techniques in addressing stability and targeting challenges associated with protein and peptide-based drugs. Chemical and enzymatic bioconjugation methods are discussed, along with crosslinking strategies for covalent attachment and site-specific conjugation approaches. The role of bioconjugation in improving stability profiles is explored, showcasing case studies that demonstrate successful stability enhancement. Furthermore, bioconjugation techniques for ligand attachment and targeting are presented, accompanied by examples of targeted protein and peptide therapeutics. The review also covers bioconjugation approaches for prolonging circulation and controlled release, focusing on strategies to extend half-life, reduce clearance, and design-controlled release systems. Analytical characterization techniques for bioconjugates, including the evaluation of conjugation efficiency, stability, and assessment of biological activity and targeting efficiency, are thoroughly examined. In vivo considerations and clinical applications of bioconjugated protein and peptide therapeutics, including pharmacokinetic and pharmacodynamic considerations, as well as preclinical and clinical developments, are discussed. Finally, the review concludes with an overview of future perspectives, emphasizing the potential for novel conjugation methods and advanced targeting strategies to further enhance the stability and targeting efficiency of protein and peptide therapeutics.
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Affiliation(s)
- Tanuja Bisht
- Department of Pharmacy, Shree Dev Bhoomi Institute of Education, Science and Technology, Veer Madho Singh Bhandari Uttarakhand Technical University, Dehradun, Uttarakhand, India
| | - Anupriya Adhikari
- Department of Pharmacy, Shree Dev Bhoomi Institute of Education, Science and Technology, Veer Madho Singh Bhandari Uttarakhand Technical University, Dehradun, Uttarakhand, India
| | - Shivanand Patil
- Department of Pharmacy, Shree Dev Bhoomi Institute of Education, Science and Technology, Veer Madho Singh Bhandari Uttarakhand Technical University, Dehradun, Uttarakhand, India
| | - Shivang Dhoundiyal
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
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13
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Xiong H, Han X, Cai L, Zheng H. Natural polysaccharides exert anti-tumor effects as dendritic cell immune enhancers. Front Oncol 2023; 13:1274048. [PMID: 37876967 PMCID: PMC10593453 DOI: 10.3389/fonc.2023.1274048] [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: 08/07/2023] [Accepted: 09/18/2023] [Indexed: 10/26/2023] Open
Abstract
With the development of immunotherapy, the process of tumor treatment is also moving forward. Polysaccharides are biological response modifiers widely found in plants, animals, fungi, and algae and are mainly composed of monosaccharides covalently linked by glycosidic bonds. For a long time, polysaccharides have been widely used clinically to enhance the body's immunity. However, their mechanisms of action in tumor immunotherapy have not been thoroughly explored. Dendritic cells (DCs) are a heterogeneous population of antigen presenting cells (APCs) that play a crucial role in the regulation and maintenance of the immune response. There is growing evidence that polysaccharides can enhance the essential functions of DCs to intervene the immune response. This paper describes the research progress on the anti-tumor immune effects of natural polysaccharides on DCs. These studies show that polysaccharides can act on pattern recognition receptors (PRRs) on the surface of DCs and activate phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), Dectin-1/Syk, and other signalling pathways, thereby promoting the main functions of DCs such as maturation, metabolism, antigen uptake and presentation, and activation of T cells, and then play an anti-tumor role. In addition, the application of polysaccharides as adjuvants for DC vaccines, in combination with adoptive immunotherapy and immune checkpoint inhibitors (ICIs), as well as their co-assembly with nanoparticles (NPs) into nano drug delivery systems is also introduced. These results reveal the biological effects of polysaccharides, provide a new perspective for the anti-tumor immunopharmacological research of natural polysaccharides, and provide helpful information for guiding polysaccharides as complementary medicines in cancer immunotherapy.
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Affiliation(s)
- Hongtai Xiong
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xinpu Han
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Liu Cai
- The First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, China
| | - Honggang Zheng
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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14
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Zandieh M, Liu J. Metal-Mediated DNA Adsorption on Carboxylated, Hydroxylated, and Hydrogenated Nanodiamonds. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2023; 39:11596-11602. [PMID: 37552885 DOI: 10.1021/acs.langmuir.3c01066] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/10/2023]
Abstract
Nanodiamonds (NDs) have attracted considerable attention owing to their quantum properties and versatility in biological applications. In this study, we systematically investigated the adsorption of DNA oligonucleotides onto NDs with three types of surface groups: carboxylated (COOH-), hydroxylated (OH-), and hydrogenated (H-). Among them, only the H-NDs showed fluorescence quenching property that is useful for real-time DNA adsorption kinetic studies. The effect of common metal ions on DNA adsorption was studied. In the presence of Na+, the order of DNA adsorption efficiency was H- > OH- > COOH-, whereas all the NDs showed a similar DNA adsorption efficiency in the presence of divalent metal ions such as Ca2+ and Zn2+. Desorption studies revealed that hydrogen bonding and metal-mediated interactions were dominant for the adsorption of DNA, and the H-NDs exhibited extraordinarily tight DNA adsorption. Finally, a fluorescently labeled DNA was adsorbed on NDs for DNA detection, and the COOH-NDs had the highest target specificity, and a detection limit of 1.4 nM was achieved. This study indicates the feasibility of using metal ions to mediate the physical adsorption of DNA to NDs and compares various NDs with graphene oxide for fundamental understanding.
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Affiliation(s)
- Mohamad Zandieh
- Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada
| | - Juewen Liu
- Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada
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15
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Gatti L, Chirizzi C, Rotta G, Milesi P, Sancho-Albero M, Sebastián V, Mondino A, Santamaría J, Metrangolo P, Chaabane L, Bombelli FB. Pivotal role of the protein corona in the cell uptake of fluorinated nanoparticles with increased sensitivity for 19F-MR imaging. NANOSCALE ADVANCES 2023; 5:3749-3760. [PMID: 37441254 PMCID: PMC10334373 DOI: 10.1039/d3na00229b] [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: 04/11/2023] [Accepted: 06/07/2023] [Indexed: 07/15/2023]
Abstract
In vivo cell tracking by non-invasive imaging technologies is needed to accelerate the clinical translation of innovative cell-based therapies. In this regard, 19F-MRI has recently gained increased attention for unbiased localization of labeled cells over time. To push forward the use of 19F-MRI for cell tracking, the development of highly performant 19F-probes is required. PLGA-based NPs containing PERFECTA, a multibranched superfluorinated molecule with an optimal MRI profile thanks to its 36 magnetically equivalent fluorine atoms, are promising 19F-MRI probes. In this work we demonstrate the importance of the surface functionalization of these NPs in relation to their interaction with the biological environment, stressing the pivotal role of the formation of the protein corona (PC) in their cellular labelling efficacy. In particular, our studies showed that the formation of PC NPs strongly promotes the cellular internalization of these NPs in microglia cells. We advocate that the formation of PC NPs in the culture medium can be a key element to be used for the optimization of cell labelling with a considerable increase of the detection sensitivity by 19F-MRI.
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Affiliation(s)
- Lodovico Gatti
- Department of Chemistry, Materials and Chemical Engineering "Giulio Natta" Politecnico di Milano, 32 Milano 20131 Italy
- Institute of Experimental Neurology (INSpe) and Experimental Imaging Center (CIS), IRCCS San Raffaele Scientific Institute Via Olgettina, 58 Milano 20132 Italy
| | - Cristina Chirizzi
- Department of Chemistry, Materials and Chemical Engineering "Giulio Natta" Politecnico di Milano, 32 Milano 20131 Italy
| | - Giulia Rotta
- Lymphocyte Activation Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute Via Olgettina, 58 Milan 20132 Italy
| | - Pietro Milesi
- Department of Chemistry, Materials and Chemical Engineering "Giulio Natta" Politecnico di Milano, 32 Milano 20131 Italy
| | - María Sancho-Albero
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza Calle Pedro Cerbuna, 12 Zaragoza 50009 Spain
- Department of Chemical Engineering and Environmental Technologies, University of Zaragoza Calle Pedro Cerbuna, 12 Zaragoza 50009 Spain
- Networking Research Center on Bioengineering Biomaterials and Nanomedicine (CIBER-BBN) Calle Monforte de Lemos, 3-5 Madrid 28029 Spain
| | - Victor Sebastián
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza Calle Pedro Cerbuna, 12 Zaragoza 50009 Spain
- Department of Chemical Engineering and Environmental Technologies, University of Zaragoza Calle Pedro Cerbuna, 12 Zaragoza 50009 Spain
- Networking Research Center on Bioengineering Biomaterials and Nanomedicine (CIBER-BBN) Calle Monforte de Lemos, 3-5 Madrid 28029 Spain
| | - Anna Mondino
- Lymphocyte Activation Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute Via Olgettina, 58 Milan 20132 Italy
| | - Jesús Santamaría
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza Calle Pedro Cerbuna, 12 Zaragoza 50009 Spain
- Department of Chemical Engineering and Environmental Technologies, University of Zaragoza Calle Pedro Cerbuna, 12 Zaragoza 50009 Spain
- Networking Research Center on Bioengineering Biomaterials and Nanomedicine (CIBER-BBN) Calle Monforte de Lemos, 3-5 Madrid 28029 Spain
| | - Pierangelo Metrangolo
- Department of Chemistry, Materials and Chemical Engineering "Giulio Natta" Politecnico di Milano, 32 Milano 20131 Italy
| | - Linda Chaabane
- Institute of Experimental Neurology (INSpe) and Experimental Imaging Center (CIS), IRCCS San Raffaele Scientific Institute Via Olgettina, 58 Milano 20132 Italy
| | - Francesca Baldelli Bombelli
- Department of Chemistry, Materials and Chemical Engineering "Giulio Natta" Politecnico di Milano, 32 Milano 20131 Italy
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16
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Muscetti O, Blal N, Mollo V, Netti PA, Guarnieri D. Intracellular Localization during Blood-Brain Barrier Crossing Influences Extracellular Release and Uptake of Fluorescent Nanoprobes. NANOMATERIALS (BASEL, SWITZERLAND) 2023; 13:1999. [PMID: 37446515 DOI: 10.3390/nano13131999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 06/23/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023]
Abstract
To improve the efficacy of nanoparticles (NPs) and boost their theragnostic potential for brain diseases, it is key to understand the mechanisms controlling blood-brain barrier (BBB) crossing. Here, the capability of 100 nm carboxylated polystyrene NPs, used as a nanoprobe model, to cross the human brain endothelial hCMEC/D3 cell layer, as well as to be consequently internalized by human brain tumor U87 cells, is investigated as a function of NPs' different intracellular localization. We compared NPs confined in the endo-lysosomal compartment, delivered to the cells through endocytosis, with free NPs in the cytoplasm, delivered by the gene gun method. The results indicate that the intracellular behavior of NPs changed as a function of their entrance mechanism. Moreover, by bypassing endo-lysosomal accumulation, free NPs were released from cells more efficiently than endocytosed NPs. Most importantly, once excreted by the endothelial cells, free NPs were released in the cell culture medium as aggregates smaller than endocytosed NPs and, consequently, they entered the human glioblastoma U87 cells more efficiently. These findings prove that intracellular localization influences NPs' long-term fate, improving their cellular release and consequent cellular uptake once in the brain parenchyma. This study represents a step forward in designing nanomaterials that are able to reach the brain effectively.
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Affiliation(s)
- Ornella Muscetti
- Center for Advanced Biomaterials for Healthcare, Istituto Italiano di Tecnologia (IIT@CRIB), Largo Barsanti e Matteucci 53, 80125 Naples, Italy
| | - Naym Blal
- Center for Advanced Biomaterials for Healthcare, Istituto Italiano di Tecnologia (IIT@CRIB), Largo Barsanti e Matteucci 53, 80125 Naples, Italy
- Dipartimento di Chimica e Biologia "Adolfo Zambelli", Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084 Salerno, Italy
| | - Valentina Mollo
- Center for Advanced Biomaterials for Healthcare, Istituto Italiano di Tecnologia (IIT@CRIB), Largo Barsanti e Matteucci 53, 80125 Naples, Italy
| | - Paolo Antonio Netti
- Center for Advanced Biomaterials for Healthcare, Istituto Italiano di Tecnologia (IIT@CRIB), Largo Barsanti e Matteucci 53, 80125 Naples, Italy
- Interdisciplinary Research Centre on Biomaterials, (CRIB), University of Naples Federico II, 80125 Naples, Italy
- Department of Chemical Materials and Industrial Production (DICMaPI), University of Naples Federico II, 80125 Naples, Italy
| | - Daniela Guarnieri
- Center for Advanced Biomaterials for Healthcare, Istituto Italiano di Tecnologia (IIT@CRIB), Largo Barsanti e Matteucci 53, 80125 Naples, Italy
- Dipartimento di Chimica e Biologia "Adolfo Zambelli", Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084 Salerno, Italy
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17
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Obeng EM, Steer DL, Fulcher AJ, Wagstaff KM. Sortase A transpeptidation produces seamless, unbranched biotinylated nanobodies for multivalent and multifunctional applications. NANOSCALE ADVANCES 2023; 5:2251-2260. [PMID: 37056610 PMCID: PMC10089078 DOI: 10.1039/d3na00014a] [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: 01/06/2023] [Accepted: 03/15/2023] [Indexed: 06/19/2023]
Abstract
Exploitation of the biotin-streptavidin interaction for advanced protein engineering is used in many bio-nanotechnology applications. As such, researchers have used diverse techniques involving chemical and enzyme reactions to conjugate biotin to biomolecules of interest for subsequent docking onto streptavidin-associated molecules. Unfortunately, the biotin-streptavidin interaction is susceptible to steric hindrance and conformational malformation, leading to random orientations that ultimately impair the function of the displayed biomolecule. To minimize steric conflicts, we employ sortase A transpeptidation to produce quantitative, seamless, and unbranched nanobody-biotin conjugates for efficient display on streptavidin-associated nanoparticles. We further characterize the protein-nanoparticle complex and demonstrate its usefulness in optical microscopy and multivalent severe acute respiratory syndrome coronavirus (SARS-CoV-2) antigen interaction. The approach reported here provides a template for making novel multivalent and multifunctional protein complexes for avidity-inspired technologies.
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Affiliation(s)
- Eugene M Obeng
- Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University Clayton VIC 3800 Australia
| | - David L Steer
- Monash Proteomics and Metabolomics Facility, Monash University Clayton VIC 3800 Australia
| | - Alex J Fulcher
- Monash Micro Imaging, Monash University Clayton VIC 3800 Australia
| | - Kylie M Wagstaff
- Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University Clayton VIC 3800 Australia
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18
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Liu M, Lai W, Chen M, Wang P, Liu J, Fang X, Yang Y, Wang C. Prominent Enhancement of Peptide-mediated Targeting Efficiency for Human Hepatocellular Carcinomas With Composition-engineered Protein Corona on Gold Nanoparticles. Colloids Surf A Physicochem Eng Asp 2023. [DOI: 10.1016/j.colsurfa.2023.131016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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19
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Percivalle NM, Carofiglio M, Conte M, Rosso G, Bentivogli A, Mesiano G, Vighetto V, Cauda V. Artificial and Naturally Derived Phospholipidic Bilayers as Smart Coatings of Solid-State Nanoparticles: Current Works and Perspectives in Cancer Therapy. Int J Mol Sci 2022; 23:ijms232415815. [PMID: 36555455 PMCID: PMC9779745 DOI: 10.3390/ijms232415815] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 11/24/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
Recent advances in nanomedicine toward cancer treatment have considered exploiting liposomes and extracellular vesicles as effective cargos to deliver therapeutic agents to tumor cells. Meanwhile, solid-state nanoparticles are continuing to attract interest for their great medical potential thanks to their countless properties and possible applications. However, possible drawbacks arising from the use of nanoparticles in nanomedicine, such as the nonspecific uptake of these materials in healthy organs, their aggregation in biological environments and their possible immunogenicity, must be taken into account. Considering these limitations and the intrinsic capability of phospholipidic bilayers to act as a biocompatible shield, their exploitation for effectively encasing solid-state nanoparticles seems a promising strategy to broaden the frontiers of cancer nanomedicine, also providing the possibility to engineer the lipid bilayers to further enhance the therapeutic potential of such nanotools. This work aims to give a comprehensive overview of the latest developments in the use of artificial liposomes and naturally derived extracellular vesicles for the coating of solid-state nanoparticles for cancer treatment, starting from in vitro works until the up-to-date advances and current limitations of these nanopharmaceutics in clinical applications, passing through in vivo and 3D cultures studies.
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20
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Xu JX, Alom MS, Yadav R, Fitzkee NC. Predicting protein function and orientation on a gold nanoparticle surface using a residue-based affinity scale. Nat Commun 2022; 13:7313. [PMID: 36437251 PMCID: PMC9701677 DOI: 10.1038/s41467-022-34749-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 11/07/2022] [Indexed: 11/28/2022] Open
Abstract
The orientation adopted by proteins on nanoparticle surfaces determines the nanoparticle's bioactivity and its interactions with living systems. Here, we present a residue-based affinity scale for predicting protein orientation on citrate-gold nanoparticles (AuNPs). Competitive binding between protein variants accounts for thermodynamic and kinetic aspects of adsorption in this scale. For hydrophobic residues, the steric considerations dominate, whereas electrostatic interactions are critical for hydrophilic residues. The scale rationalizes the well-defined binding orientation of the small GB3 protein, and it subsequently predicts the orientation and active site accessibility of two enzymes on AuNPs. Additionally, our approach accounts for the AuNP-bound activity of five out of six additional enzymes from the literature. The model developed here enables high-throughput predictions of protein behavior on nanoparticles, and it enhances our understanding of protein orientation in the biomolecular corona, which should greatly enhance the performance and safety of nanomedicines used in vivo.
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Affiliation(s)
- Joanna Xiuzhu Xu
- Department of Chemistry, Mississippi State University, Mississippi State, MS, 39762, USA
| | - Md Siddik Alom
- Department of Chemistry, Mississippi State University, Mississippi State, MS, 39762, USA
| | - Rahul Yadav
- Department of Chemistry, Mississippi State University, Mississippi State, MS, 39762, USA
| | - Nicholas C Fitzkee
- Department of Chemistry, Mississippi State University, Mississippi State, MS, 39762, USA.
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21
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Elasticity regulates nanomaterial transport as delivery vehicles: Design, characterization, mechanisms and state of the art. Biomaterials 2022; 291:121879. [DOI: 10.1016/j.biomaterials.2022.121879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 10/14/2022] [Accepted: 10/23/2022] [Indexed: 11/22/2022]
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22
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Yang T, Zhai J, Hu D, Yang R, Wang G, Li Y, Liang G. "Targeting Design" of Nanoparticles in Tumor Therapy. Pharmaceutics 2022; 14:pharmaceutics14091919. [PMID: 36145668 PMCID: PMC9501451 DOI: 10.3390/pharmaceutics14091919] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 09/01/2022] [Accepted: 09/06/2022] [Indexed: 11/22/2022] Open
Abstract
Tumor-targeted therapy based on nanoparticles is a popular research direction in the biomedical field. After decades of research and development, both the passive targeting ability of the inherent properties of NPs and the active targeting based on ligand receptor interaction have gained deeper understanding. Unfortunately, most targeted delivery strategies are still in the preclinical trial stage, so it is necessary to further study the biological fate of particles in vivo and the interaction mechanism with tumors. This article reviews different targeted delivery strategies based on NPs, and focuses on the physical and chemical properties of NPs (size, morphology, surface and intrinsic properties), ligands (binding number/force, activity and species) and receptors (endocytosis, distribution and recycling) and other factors that affect particle targeting. The limitations and solutions of these factors are further discussed, and a variety of new targeting schemes are introduced, hoping to provide guidance for future targeting design and achieve the purpose of rapid transformation of targeted particles into clinical application.
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Affiliation(s)
- Tingting Yang
- School of Basic Medical Sciences, Henan University of Science & Technology, Luoyang 471023, China
| | - Jingming Zhai
- Department of General Surgery, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science & Technology, Luoyang 471003, China
| | - Dong Hu
- School of Basic Medical Sciences, Henan University of Science & Technology, Luoyang 471023, China
| | - Ruyue Yang
- School of Basic Medical Sciences, Henan University of Science & Technology, Luoyang 471023, China
| | - Guidan Wang
- School of Basic Medical Sciences, Henan University of Science & Technology, Luoyang 471023, China
| | - Yuanpei Li
- School of Basic Medical Sciences, Henan University of Science & Technology, Luoyang 471023, China
- Correspondence: (Y.L.); (G.L.)
| | - Gaofeng Liang
- School of Basic Medical Sciences, Henan University of Science & Technology, Luoyang 471023, China
- Correspondence: (Y.L.); (G.L.)
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23
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Rhaman MM, Islam MR, Akash S, Mim M, Noor alam M, Nepovimova E, Valis M, Kuca K, Sharma R. Exploring the role of nanomedicines for the therapeutic approach of central nervous system dysfunction: At a glance. Front Cell Dev Biol 2022; 10:989471. [PMID: 36120565 PMCID: PMC9478743 DOI: 10.3389/fcell.2022.989471] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 08/08/2022] [Indexed: 12/12/2022] Open
Abstract
In recent decades, research scientists, molecular biologists, and pharmacologists have placed a strong emphasis on cutting-edge nanostructured materials technologies to increase medicine delivery to the central nervous system (CNS). The application of nanoscience for the treatment of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), Huntington’s disease (HD), brain cancer, and hemorrhage has the potential to transform care. Multiple studies have indicated that nanomaterials can be used to successfully treat CNS disorders in the case of neurodegeneration. Nanomedicine development for the cure of degenerative and inflammatory diseases of the nervous system is critical. Nanoparticles may act as a drug transporter that can precisely target sick brain sub-regions, boosting therapy success. It is important to develop strategies that can penetrate the blood–brain barrier (BBB) and improve the effectiveness of medications. One of the probable tactics is the use of different nanoscale materials. These nano-based pharmaceuticals offer low toxicity, tailored delivery, high stability, and drug loading capacity. They may also increase therapeutic effectiveness. A few examples of the many different kinds and forms of nanomaterials that have been widely employed to treat neurological diseases include quantum dots, dendrimers, metallic nanoparticles, polymeric nanoparticles, carbon nanotubes, liposomes, and micelles. These unique qualities, including sensitivity, selectivity, and ability to traverse the BBB when employed in nano-sized particles, make these nanoparticles useful for imaging studies and treatment of NDs. Multifunctional nanoparticles carrying pharmacological medications serve two purposes: they improve medication distribution while also enabling cell dynamics imaging and pharmacokinetic study. However, because of the potential for wide-ranging clinical implications, safety concerns persist, limiting any potential for translation. The evidence for using nanotechnology to create drug delivery systems that could pass across the BBB and deliver therapeutic chemicals to CNS was examined in this study.
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Affiliation(s)
- Md. Mominur Rhaman
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
- *Correspondence: Md. Mominur Rhaman, ; Rohit Sharma,
| | - Md. Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Shopnil Akash
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Mobasharah Mim
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Md. Noor alam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Eugenie Nepovimova
- Department of Chemistry, Faculty of Science, University of Hradec Králové, Hradec Králové, Czech Republic
| | - Martin Valis
- Department of Neurology, Charles University in Prague, Faculty of Medicine in Hradec Králové and University Hospital, Hradec Králové, Czech Republic
| | - Kamil Kuca
- Department of Chemistry, Faculty of Science, University of Hradec Králové, Hradec Králové, Czech Republic
- Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI), University of Granada, Granada, Spain
| | - Rohit Sharma
- Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
- *Correspondence: Md. Mominur Rhaman, ; Rohit Sharma,
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24
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Niknam Z, Hosseinzadeh F, Shams F, Fath-Bayati L, Nuoroozi G, Mohammadi Amirabad L, Mohebichamkhorami F, Khakpour Naeimi S, Ghafouri-Fard S, Zali H, Tayebi L, Rasmi Y. Recent advances and challenges in graphene-based nanocomposite scaffolds for tissue engineering application. J Biomed Mater Res A 2022; 110:1695-1721. [PMID: 35762460 DOI: 10.1002/jbm.a.37417] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 05/22/2022] [Accepted: 06/08/2022] [Indexed: 02/06/2023]
Abstract
Graphene-based nanocomposites have recently attracted increasing attention in tissue engineering because of their extraordinary features. These biocompatible substances, in the presence of an apt microenvironment, can stimulate and sustain the growth and differentiation of stem cells into different lineages. This review discusses the characteristics of graphene and its derivatives, such as their excellent electrical signal transduction, carrier mobility, outstanding mechanical strength with improving surface characteristics, self-lubrication, antiwear properties, enormous specific surface area, and ease of functional group modification. Moreover, safety issues in the application of graphene and its derivatives in terms of biocompatibility, toxicity, and interaction with immune cells are discussed. We also describe the applicability of graphene-based nanocomposites in tissue healing and organ regeneration, particularly in the bone, cartilage, teeth, neurons, heart, skeletal muscle, and skin. The impacts of special textural and structural characteristics of graphene-based nanomaterials on the regeneration of various tissues are highlighted. Finally, the present review gives some hints on future research for the transformation of these exciting materials in clinical studies.
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Affiliation(s)
- Zahra Niknam
- Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.,Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Faezeh Hosseinzadeh
- Department of Tissue Engineering, Qom University of Medical Science, Qom, Iran.,Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
| | - Forough Shams
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Leyla Fath-Bayati
- Department of Tissue Engineering, Qom University of Medical Science, Qom, Iran
| | - Ghader Nuoroozi
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Fariba Mohebichamkhorami
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hakimeh Zali
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Lobat Tayebi
- Marquette University School of Dentistry, Milwaukee, Wisconsin, USA
| | - Yousef Rasmi
- Department of Clinical Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.,Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran
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25
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Dynamic intracellular exchange of nanomaterials' protein corona perturbs proteostasis and remodels cell metabolism. Proc Natl Acad Sci U S A 2022; 119:e2200363119. [PMID: 35653569 DOI: 10.1073/pnas.2200363119] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
SignificanceThis study analyzed the dynamic protein corona on the surface of nanoparticles as they traversed from blood to cell lysosomes and escaped from lysosomes to cytoplasm in the target cells. We found with proteomic analysis an abundance of chaperone and glycolysis coronal proteins (i.e., heat shock cognate protein 70, heat shock protein 90, and pyruvate kinase M2 [PKM2]) after escape of the nanoparticles from lysosomes to the cytosol. Alterations of the coronal proteins (e.g., PKM2 and chaperone binding) induced proteostasis collapse, which subsequently led to elevated chaperone-mediated autophagy (CMA) activity in cells. As PKM2 is a key molecule in cell metabolism, we also revealed that PKM2 depletion was causative to CMA-induced cell metabolism disruption from glycolysis to lipid metabolism.
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26
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Gao X, Xu J, Yao T, Liu X, Zhang H, Zhan C. Peptide-decorated nanocarriers penetrating the blood-brain barrier for imaging and therapy of brain diseases. Adv Drug Deliv Rev 2022; 187:114362. [PMID: 35654215 DOI: 10.1016/j.addr.2022.114362] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 05/11/2022] [Accepted: 05/25/2022] [Indexed: 12/12/2022]
Abstract
Blood-Brain Barrier (BBB) is one of the most important physiological barriers strictly restricting the substance exchange between blood and brain tissues. While the BBB protects the brain from infections and toxins and maintains brain homeostasis, it is also recognized as the main obstacle to the penetration of therapeutics and imaging agents into the brain. Due to high specificity and affinity, peptides are frequently exploited to decorate nanocarriers across the BBB for diagnosis and/or therapy purposes. However, there are still some challenges that restrict their clinical application, such as stability, safety and immunocompatibility. In this review, we summarize the biological and pathophysiological characteristics of the BBB, strategies across the BBB, and recent progress on peptide decorated nanocarriers for brain diseases diagnosis and therapy. The challenges and opportunities for their translation are also discussed.
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27
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Vène E, Jarnouen K, Ribault C, Vlach M, Verres Y, Bourgeois M, Lepareur N, Cammas-Marion S, Loyer P. Circumsporozoite Protein of Plasmodium berghei- and George Baker Virus A-Derived Peptides Trigger Efficient Cell Internalization of Bioconjugates and Functionalized Poly(ethylene glycol)- b-poly(benzyl malate)-Based Nanoparticles in Human Hepatoma Cells. Pharmaceutics 2022; 14:804. [PMID: 35456637 PMCID: PMC9028075 DOI: 10.3390/pharmaceutics14040804] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 03/31/2022] [Accepted: 04/03/2022] [Indexed: 02/04/2023] Open
Abstract
In order to identify the peptides, selected from the literature, that exhibit the strongest tropism towards human hepatoma cells, cell uptake assays were performed using biotinylated synthetic peptides bound to fluorescent streptavidin or engrafted onto nanoparticles (NPs), prepared from biotin-poly(ethylene glycol)-block-poly(benzyl malate) (Biot-PEG-b-PMLABe) via streptavidin bridging. Two peptides, derived from the circumsporozoite protein of Plasmodium berghei- (CPB) and George Baker (GB) Virus A (GBVA10-9), strongly enhanced the endocytosis of both streptavidin conjugates and NPs in hepatoma cells, compared to primary human hepatocytes and non-hepatic cells. Unexpectedly, the uptake of CPB- and GBVA10-9 functionalized PEG-b-PMLABe-based NPs by hepatoma cells involved, at least in part, the peptide binding to apolipoproteins, which would promote NP's interactions with cell membrane receptors of HDL particles. In addition, CPB and GBVA10-9 peptide-streptavidin conjugates favored the uptake by hepatoma cells over that of the human macrophages, known to strongly internalize nanoparticles by phagocytosis. These two peptides are promising candidate ligands for targeting hepatocellular carcinomas.
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Affiliation(s)
- Elise Vène
- Institut NUMECAN (Nutrition Metabolisms and Cancer), Inserm, UMR-S 1241, INRAE UMR-A 1341, Univ Rennes, F-35000 Rennes, France; (E.V.); (K.J.); (C.R.); (M.V.); (Y.V.)
- Pôle Pharmacie, Service Hospitalo-Universitaire de Pharmacie, CHU Rennes, F-35033 Rennes, France
| | - Kathleen Jarnouen
- Institut NUMECAN (Nutrition Metabolisms and Cancer), Inserm, UMR-S 1241, INRAE UMR-A 1341, Univ Rennes, F-35000 Rennes, France; (E.V.); (K.J.); (C.R.); (M.V.); (Y.V.)
| | - Catherine Ribault
- Institut NUMECAN (Nutrition Metabolisms and Cancer), Inserm, UMR-S 1241, INRAE UMR-A 1341, Univ Rennes, F-35000 Rennes, France; (E.V.); (K.J.); (C.R.); (M.V.); (Y.V.)
| | - Manuel Vlach
- Institut NUMECAN (Nutrition Metabolisms and Cancer), Inserm, UMR-S 1241, INRAE UMR-A 1341, Univ Rennes, F-35000 Rennes, France; (E.V.); (K.J.); (C.R.); (M.V.); (Y.V.)
- INRAE, Institut AGRO, PEGASE UMR 1348, F-35590 Saint-Gilles, France
| | - Yann Verres
- Institut NUMECAN (Nutrition Metabolisms and Cancer), Inserm, UMR-S 1241, INRAE UMR-A 1341, Univ Rennes, F-35000 Rennes, France; (E.V.); (K.J.); (C.R.); (M.V.); (Y.V.)
| | - Mickaël Bourgeois
- CRCINA, Inserm, CNRS, Université de Nantes, F-44000 Nantes, France;
- ARRONAX Cyclotron, F-44817 Saint Herblain, France
| | - Nicolas Lepareur
- Institut NUMECAN (Nutrition Metabolisms and Cancer), Inserm, UMR-S 1241, INRAE UMR-A 1341, Univ Rennes, F-35000 Rennes, France; (E.V.); (K.J.); (C.R.); (M.V.); (Y.V.)
- Comprehensive Cancer Center Eugène Marquis, F-35000 Rennes, France
| | - Sandrine Cammas-Marion
- Institut NUMECAN (Nutrition Metabolisms and Cancer), Inserm, UMR-S 1241, INRAE UMR-A 1341, Univ Rennes, F-35000 Rennes, France; (E.V.); (K.J.); (C.R.); (M.V.); (Y.V.)
- Institut des Sciences Chimiques de Rennes (ISCR), Ecole Nationale Supérieure de Chimie de Rennes, CNRS UMR 6226, University of Rennes, F-35042 Rennes, France
| | - Pascal Loyer
- Institut NUMECAN (Nutrition Metabolisms and Cancer), Inserm, UMR-S 1241, INRAE UMR-A 1341, Univ Rennes, F-35000 Rennes, France; (E.V.); (K.J.); (C.R.); (M.V.); (Y.V.)
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28
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Berger S, Berger M, Bantz C, Maskos M, Wagner E. Performance of nanoparticles for biomedical applications: The in vitro/ in vivo discrepancy. BIOPHYSICS REVIEWS 2022; 3:011303. [PMID: 38505225 PMCID: PMC10903387 DOI: 10.1063/5.0073494] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 01/04/2022] [Indexed: 03/21/2024]
Abstract
Nanomedicine has a great potential to revolutionize the therapeutic landscape. However, up-to-date results obtained from in vitro experiments predict the in vivo performance of nanoparticles weakly or not at all. There is a need for in vitro experiments that better resemble the in vivo reality. As a result, animal experiments can be reduced, and potent in vivo candidates will not be missed. It is important to gain a deeper knowledge about nanoparticle characteristics in physiological environment. In this context, the protein corona plays a crucial role. Its formation process including driving forces, kinetics, and influencing factors has to be explored in more detail. There exist different methods for the investigation of the protein corona and its impact on physico-chemical and biological properties of nanoparticles, which are compiled and critically reflected in this review article. The obtained information about the protein corona can be exploited to optimize nanoparticles for in vivo application. Still the translation from in vitro to in vivo remains challenging. Functional in vitro screening under physiological conditions such as in full serum, in 3D multicellular spheroids/organoids, or under flow conditions is recommended. Innovative in vivo screening using barcoded nanoparticles can simultaneously test more than hundred samples regarding biodistribution and functional delivery within a single mouse.
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Affiliation(s)
- Simone Berger
- Pharmaceutical Biotechnology, Department of Pharmacy, Ludwig–Maximilians-Universität (LMU) Munich, Butenandtstr. 5-13, D-81377 Munich, Germany
| | - Martin Berger
- Department of Chemistry, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany
| | - Christoph Bantz
- Fraunhofer Institute for Microengineering and Microsystems IMM, Carl-Zeiss-Str. 18-20, D-55129 Mainz, Germany
| | | | - Ernst Wagner
- Pharmaceutical Biotechnology, Department of Pharmacy, Ludwig–Maximilians-Universität (LMU) Munich, Butenandtstr. 5-13, D-81377 Munich, Germany
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29
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Smart Bioinks for the Printing of Human Tissue Models. Biomolecules 2022; 12:biom12010141. [PMID: 35053289 PMCID: PMC8773823 DOI: 10.3390/biom12010141] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 01/05/2022] [Accepted: 01/13/2022] [Indexed: 12/11/2022] Open
Abstract
3D bioprinting has tremendous potential to revolutionize the field of regenerative medicine by automating the process of tissue engineering. A significant number of new and advanced bioprinting technologies have been developed in recent years, enabling the generation of increasingly accurate models of human tissues both in the healthy and diseased state. Accordingly, this technology has generated a demand for smart bioinks that can enable the rapid and efficient generation of human bioprinted tissues that accurately recapitulate the properties of the same tissue found in vivo. Here, we define smart bioinks as those that provide controlled release of factors in response to stimuli or combine multiple materials to yield novel properties for the bioprinting of human tissues. This perspective piece reviews the existing literature and examines the potential for the incorporation of micro and nanotechnologies into bioinks to enhance their properties. It also discusses avenues for future work in this cutting-edge field.
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30
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Mollé LM, Smyth CH, Yuen D, Johnston APR. Nanoparticles for vaccine and gene therapy: Overcoming the barriers to nucleic acid delivery. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2022; 14:e1809. [PMID: 36416028 PMCID: PMC9786906 DOI: 10.1002/wnan.1809] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 04/19/2022] [Accepted: 04/24/2022] [Indexed: 11/24/2022]
Abstract
Nucleic acid therapeutics can be used to control virtually every aspect of cell behavior and therefore have significant potential to treat genetic disorders, infectious diseases, and cancer. However, while clinically approved to treat a small number of diseases, the full potential of nucleic acid therapeutics is hampered by inefficient delivery. Nucleic acids are large, highly charged biomolecules that are sensitive to degradation and so the approaches to deliver these molecules differ significantly from traditional small molecule drugs. Current studies suggest less than 1% of the injected nucleic acid dose is delivered to the target cell in an active form. This inefficient delivery increases costs and limits their use to applications where a small amount of nucleic acid is sufficient. In this review, we focus on two of the major barriers to efficient nucleic acid delivery: (1) delivery to the target cell and (2) transport to the subcellular compartment where the nucleic acids are therapeutically active. We explore how nanoparticles can be modified with targeting ligands to increase accumulation in specific cells, and how the composition of the nanoparticle can be engineered to manipulate or disrupt cellular membranes and facilitate delivery to the optimal subcellular compartments. Finally, we highlight how with intelligent material design, nanoparticle delivery systems have been developed to deliver nucleic acids that silence aberrant genes, correct genetic mutations, and act as both therapeutic and prophylactic vaccines. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Lipid-Based Structures.
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Affiliation(s)
- Lara M. Mollé
- Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleVictoriaAustralia
| | - Cameron H. Smyth
- Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleVictoriaAustralia
| | - Daniel Yuen
- Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleVictoriaAustralia
| | - Angus P. R. Johnston
- Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleVictoriaAustralia
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31
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Mills-Goodlet R, Johnson L, Hoppe IJ, Regl C, Geppert M, Schenck M, Huber S, Hauser M, Ferreira F, Hüsing N, Huber CG, Brandstetter H, Duschl A, Himly M. The nanotopography of SiO 2 particles impacts the selectivity and 3D fold of bound allergens. NANOSCALE 2021; 13:20508-20520. [PMID: 34854455 PMCID: PMC8675021 DOI: 10.1039/d1nr05958k] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 11/06/2021] [Indexed: 06/13/2023]
Abstract
A detailed description of the changes that occur during the formation of protein corona represents a fundamental question in nanoscience, given that it not only impacts the behaviour of nanoparticles but also affects the bound proteins. Relevant questions include whether proteins selectively bind particles, whether a specific orientation is preferred for binding, and whether particle binding leads to a modulation of their 3D fold. For allergens, it is important to answer these questions given that all these effects can modify the allergenic response of atopic individuals. These potential impacts on the bound allergen are closely related to the specific properties of the involved nanoparticles. One important property influencing the formation of protein corona is the nanotopography of the particles. Herein, we studied the effect of nanoparticle porosity on allergen binding using mesoporous and non-porous SiO2 NPs. We investigated (i) the selectivity of allergen binding from a mixture such as crude pollen extract, (ii) whether allergen binding results in a preferred orientation, (iii) the influence of binding on the conformation of the allergen, and (iv) how the binding affects the allergenic response. Nanotopography was found to play a major role in the formation of protein corona, impacting the physicochemical and biological properties of the NP-bound allergen. The porosity of the surface of the SiO2 nanoparticles resulted in a higher binding capacity with pronounced selectivity for (preferentially) binding the major birch pollen allergen Bet v 1. Furthermore, the binding of Bet v 1 to the mesoporous rather than the non-porous SiO2 nanoparticles influenced the 3D fold of the protein, resulting in at least partial unfolding. Consequently, this conformational change influenced the allergenic response, as observed by mediator release assays employing the sera of patients and immune effector cells. For an in-depth understanding of the bio-nano interactions, the properties of the particles need to be considered not only regarding the identity and morphology of the material, but also their nanotopography, given that porosity may greatly influence the structure, and hence the biological behaviour of the bound proteins. Thus, thorough structural investigations upon the formation of protein corona are important when considering immunological outcomes, as particle binding can influence the allergenic response elicited by the bound allergen.
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Affiliation(s)
| | - Litty Johnson
- Dept. Biosciences, Paris Lodron University of Salzburg, Austria.
| | - Isabel J Hoppe
- Dept. Biosciences, Paris Lodron University of Salzburg, Austria.
- Christian Doppler Laboratory for Innovative Tools for Biosimilar Characterization, Paris Lodron University of Salzburg, Austria
| | - Christof Regl
- Dept. Biosciences, Paris Lodron University of Salzburg, Austria.
| | - Mark Geppert
- Dept. Biosciences, Paris Lodron University of Salzburg, Austria.
| | - Milena Schenck
- Dept. Chemistry and Physics of Materials, Paris Lodron University of Salzburg, Austria
| | - Sara Huber
- Dept. Biosciences, Paris Lodron University of Salzburg, Austria.
| | - Michael Hauser
- Dept. Biosciences, Paris Lodron University of Salzburg, Austria.
| | - Fátima Ferreira
- Dept. Biosciences, Paris Lodron University of Salzburg, Austria.
| | - Nicola Hüsing
- Dept. Chemistry and Physics of Materials, Paris Lodron University of Salzburg, Austria
| | - Christian G Huber
- Dept. Biosciences, Paris Lodron University of Salzburg, Austria.
- Christian Doppler Laboratory for Innovative Tools for Biosimilar Characterization, Paris Lodron University of Salzburg, Austria
| | - Hans Brandstetter
- Dept. Biosciences, Paris Lodron University of Salzburg, Austria.
- Christian Doppler Laboratory for Innovative Tools for Biosimilar Characterization, Paris Lodron University of Salzburg, Austria
| | - Albert Duschl
- Dept. Biosciences, Paris Lodron University of Salzburg, Austria.
| | - Martin Himly
- Dept. Biosciences, Paris Lodron University of Salzburg, Austria.
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Wang LM, Wang YT, Yang WX. Engineered nanomaterials induce alterations in biological barriers: focus on paracellular permeability. Nanomedicine (Lond) 2021; 16:2725-2741. [PMID: 34870452 DOI: 10.2217/nnm-2021-0165] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Engineered nanoparticles (ENPs) are widely used in medical diagnosis and treatment, as food additives and as energy materials. ENPs may exert adverse or beneficial effects on the human body, which may be linked to interactions with biological barriers. In this review, the authors summarize the influences of four typical metal/metal oxide nanomaterials (Ag, TiO2, Au, ZnO nanoparticles) on the paracellular permeability of biological barriers. Disruptions on tight junctions, adhesion junctions, gap junctions and desmosomes via complex signaling pathways, such as the MAPK, PKC and ROCK signaling pathways, affect paracellular permeability. Reactive oxygen species and cytokines underlie the mechanism of ENP-triggered alterations in paracellular permeability. This review provides the information necessary for the cautious application of nanoparticles in medicine and life sciences in the future.
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Affiliation(s)
- Lan-Min Wang
- The Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou, 310058, PR China
| | - Yu-Ting Wang
- The Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou, 310058, PR China
| | - Wan-Xi Yang
- The Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou, 310058, PR China
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Grace VMB, Wilson DD, Guruvayoorappan C, Danisha JP, Bonati L. Liposome nano-formulation with cationic polar lipid DOTAP and cholesterol as a suitable pH-responsive carrier for molecular therapeutic drug (all-trans retinoic acid) delivery to lung cancer cells. IET Nanobiotechnol 2021; 15:380-390. [PMID: 34694713 PMCID: PMC8675848 DOI: 10.1049/nbt2.12028] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 12/27/2020] [Accepted: 01/17/2021] [Indexed: 12/13/2022] Open
Abstract
The molecular targeted drug ATRA demands a suitable carrier that delivers to the cancer site due to its poor bioavailability and drug resistance. ATRA, being a lipid with carboxylic acid, has been nano‐formulated as a cationic lipo‐ATRA with DOTAP:cholesterol:ATRA (5:4:1) and its pH‐responsive release, intracellular drug accumulation, and anticancer effect on human lung cancer (A549) cell line analysed. The analysis of the physicochemical characteristics of the developed lipo‐ATRA (0.8 µmol) revealed that the size of 231 ± 2.35 d.nm had a zeta potential of 6.4 ± 1.19 and an encapsulation efficiency of 93.7 ± 3.6%. The ATRA release from lipo‐ATRA in vitro was significantly (p ≤ 0.05) higher at acidic pH 6 compared to pH 7.5. The intracellular uptake of ATRA into lipo‐ATRA‐treated A549 cells was seven‐fold higher (0.007 ± 0.001 mg/ml) while only three‐fold uptake was observed in free ATRA treatment (0.003 ± 0.002 mg/ml). The lipo‐ATRA treatment caused a highly significant (p ≤ 0.001) decrease in percent cell viability at 48 h when compared with the free ATRA treatment. Overall, the results proved that the developed lipo‐ATRA has suitable physicochemical properties with enhanced ATRA release at acidic pH, while maintaining stability at physiologic pH and temperature. This resulted in an increased ATRA uptake by lung cancer cells with enhanced treatment efficiency. Hence, it is concluded that DOTAP lipo‐ATRA is a suitable carrier for ATRA delivery to solid cancer cells.
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Affiliation(s)
| | - Devarajan David Wilson
- School of Science, Arts, Media and Management, Karunya Institute of Technology and Sciences, Coimbatore, Tamil Nadu, India
| | - Chandrasekharan Guruvayoorappan
- Laboratory of Immunopharmacology and Experimental Therapeutics, Division of Cancer Research, Regional Cancer Centre, Medical College Campus, Thiruvananthapuram, Kerala, India
| | - Jesubatham Perinba Danisha
- Department of Biotechnology, Karunya Institute of Technology and Sciences, Coimbatore, Tamil Nadu, India
| | - Lucia Bonati
- IAESTE Intern at Department of Biotechnology, Karunya Institute of Technology and Sciences, Coimbatore, Tamil Nadu, India
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Sommi P, Vitali A, Coniglio S, Callegari D, Barbieri S, Casu A, Falqui A, Vigano’ L, Vigani B, Ferrari F, Anselmi-Tamburini U. Microvilli Adhesion: An Alternative Route for Nanoparticle Cell Internalization. ACS NANO 2021; 15:15803-15814. [PMID: 34585565 PMCID: PMC8552441 DOI: 10.1021/acsnano.1c03151] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 09/24/2021] [Indexed: 05/31/2023]
Abstract
The cellular uptake of nanoparticles (NPs) represents a critical step in nanomedicine and a crucial point for understanding the interaction of nanomaterials with biological systems. No specific mechanism of uptake has been identified so far, as the NPs are generally incorporated by the cells through one of the few well-known endocytotic mechanisms. Here, an alternative internalization route mediated by microvilli adhesion is demonstrated. This microvillus-mediated adhesion (MMA) has been observed using ceria and magnetite NPs with a dimension of <40 nm functionalized with polyacrylic acid but not using NPs with a neutral or positive functionalization. Such an adhesion was not cell specific, as it was demonstrated in three different cell lines. MMA was also reduced by modifications of the microvillus lipid rafts, obtained by depleting cholesterol and altering synthesis of sphingolipids. We found a direct relationship between MAA, cell cycle, and density of microvilli. The evidence suggests that MMA differs from the commonly described uptake mechanisms and might represent an interesting alternative approach for selective NP delivery.
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Affiliation(s)
- Patrizia Sommi
- Human
Physiology Unit, Department of Molecular Medicine, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy
| | - Agostina Vitali
- Department
of Chemistry, University of Pavia, 27100 Pavia, Italy
| | - Stefania Coniglio
- Human
Physiology Unit, Department of Molecular Medicine, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy
| | | | - Sofia Barbieri
- Department
of Physics, University of Pavia, 27100 Pavia, Italy
| | - Alberto Casu
- Biological
and Environmental Sciences and Engineering Division, NABLA Lab, King Abdullah University of Science and Technology
(KAUST), 23955-6900 Thuwal, Saudi Arabia
| | - Andrea Falqui
- Biological
and Environmental Sciences and Engineering Division, NABLA Lab, King Abdullah University of Science and Technology
(KAUST), 23955-6900 Thuwal, Saudi Arabia
| | - Lorenzo Vigano’
- Department
of Chemistry, University of Pavia, 27100 Pavia, Italy
| | - Barbara Vigani
- Department
of Drug Sciences, University of Pavia, 27100 Pavia, Italy
| | - Franca Ferrari
- Department
of Drug Sciences, University of Pavia, 27100 Pavia, Italy
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Akhter MH, Khalilullah H, Gupta M, Alfaleh MA, Alhakamy NA, Riadi Y, Md S. Impact of Protein Corona on the Biological Identity of Nanomedicine: Understanding the Fate of Nanomaterials in the Biological Milieu. Biomedicines 2021; 9:1496. [PMID: 34680613 PMCID: PMC8533425 DOI: 10.3390/biomedicines9101496] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 10/11/2021] [Accepted: 10/13/2021] [Indexed: 12/15/2022] Open
Abstract
Nanoparticles (NPs) in contact with a biological medium are rapidly comprehended by a number of protein molecules resulting in the formation of an NP-protein complex called protein corona (PC). The cell sees the protein-coated NPs as the synthetic identity is masked by protein surfacing. The PC formation ultimately has a substantial impact on various biological processes including drug release, drug targeting, cell recognition, biodistribution, cellular uptake, and therapeutic efficacy. Further, the composition of PC is largely influenced by the physico-chemical properties of NPs viz. the size, shape, surface charge, and surface chemistry in the biological milieu. However, the change in the biological responses of the new substrate depends on the quantity of protein access by the NPs. The PC-layered NPs act as new biological entities and are recognized as different targeting agents for the receptor-mediated ingress of therapeutics in the biological cells. The corona-enveloped NPs have both pros and cons in the biological system. The review provides a brief insight into the impact of biomolecules on nanomaterials carrying cargos and their ultimate fate in the biological milieu.
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Affiliation(s)
- Md Habban Akhter
- School of Pharmaceutical and Population Health Informatics (SoPPHI), DIT University, Dehradun 248009, India
| | - Habibullah Khalilullah
- Department of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Unaizah 51911, Saudi Arabia;
| | - Manish Gupta
- Department of Pharmaceutical Sciences, School of Health Sciences, University of Petroleum and Energy Studies (UPES), Dehradun 248007, India;
| | - Mohamed A. Alfaleh
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (M.A.A.); (N.A.A.)
- King Fahd Medical Research Center, Vaccines and Immunotherapy Unit, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Nabil A. Alhakamy
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (M.A.A.); (N.A.A.)
- Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Yassine Riadi
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia;
| | - Shadab Md
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (M.A.A.); (N.A.A.)
- Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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36
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Prospero AG, Buranello LP, Fernandes CA, Dos Santos LD, Soares G, C Rossini B, Zufelato N, Bakuzis AF, de Mattos Fontes MR, de Arruda Miranda JR. Corona protein impacts on alternating current biosusceptometry signal and circulation times of differently coated MnFe 2O 4 nanoparticles. Nanomedicine (Lond) 2021; 16:2189-2206. [PMID: 34533056 DOI: 10.2217/nnm-2021-0195] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background: We evaluated the impacts of corona protein (CP) formation on the alternating current biosusceptometry (ACB) signal intensity and in vivo circulation times of three differently coated magnetic nanoparticles (MNP): bare, citrate-coated and bovine serum albumin-coated MNPs. Methods: We employed the ACB system, gel electrophoresis and mass spectrometry analysis. Results: Higher CP formation led to a greater reduction in the in vitro ACB signal intensity and circulation time. We found fewer proteins forming the CP for the bovine serum albumin-coated MNPs, which presented the highest circulation time in vivo among the MNPs studied. Conclusion: These data showed better biocompatibility, stability and magnetic signal uniformity in biological media for bovine serum albumin-coated MNPs than for citrate-coated MNPs and bare MNPs.
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Affiliation(s)
- Andre Gonçalves Prospero
- Department of Biophysics and Pharmacology, São Paulo State University, Botucatu, São Paulo, 18618-689, Brazil
| | - Lais Pereira Buranello
- Department of Biophysics and Pharmacology, São Paulo State University, Botucatu, São Paulo, 18618-689, Brazil
| | - Carlos Ah Fernandes
- Department of Biophysics and Pharmacology, São Paulo State University, Botucatu, São Paulo, 18618-689, Brazil.,Museum National d'Histoire Naturelle, Institut de Minéralogie, Physique des Matériaux et Cosmochimie, IMPMC, Sorbonne Université, UMR 7590, CNRS, Paris, France
| | - Lucilene Delazari Dos Santos
- Graduate Program in Tropical Diseases, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu, São Paulo, 18618-687, Brazil.,Biotechnology Institute, São Paulo State University, Botucatu, São Paulo, 18607-440, Brazil
| | - Guilherme Soares
- Department of Biophysics and Pharmacology, São Paulo State University, Botucatu, São Paulo, 18618-689, Brazil
| | - Bruno C Rossini
- Biotechnology Institute, São Paulo State University, Botucatu, São Paulo, 18607-440, Brazil
| | - Nícholas Zufelato
- Institute of Physics and CNanoMed, Federal University of Goiás, Goiânia, 74690-900, Brazil
| | | | - Marcos R de Mattos Fontes
- Department of Biophysics and Pharmacology, São Paulo State University, Botucatu, São Paulo, 18618-689, Brazil
| | - José R de Arruda Miranda
- Department of Biophysics and Pharmacology, São Paulo State University, Botucatu, São Paulo, 18618-689, Brazil
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37
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Sully RE, Moore CJ, Garelick H, Loizidou E, Podoleanu AG, Gubala V. Nanomedicines and microneedles: a guide to their analysis and application. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2021; 13:3326-3347. [PMID: 34313266 DOI: 10.1039/d1ay00954k] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
The fast-advancing progress in the research of nanomedicine and microneedle applications in the past two decades has suggested that the combination of the two concepts could help to overcome some of the challenges we are facing in healthcare. They include poor patient compliance with medication and the lack of appropriate administration forms that enable the optimal dose to reach the target site. Nanoparticles as drug vesicles can protect their cargo and deliver it to the target site, while evading the body's defence mechanisms. Unfortunately, despite intense research on nanomedicine in the past 20 years, we still haven't answered some crucial questions, e.g. about their colloidal stability in solution and their optimal formulation, which makes the translation of this exciting technology from the lab bench to a viable product difficult. Dissolvable microneedles could be an effective way to maintain and stabilise nano-sized formulations, whilst enhancing the ability of nanoparticles to penetrate the stratum corneum barrier. Both concepts have been individually investigated fairly well and many analytical techniques for tracking the fate of nanomaterials with their precious cargo, both in vitro and in vivo, have been established. Yet, to the best of our knowledge, a comprehensive overview of the analytical tools encompassing the concepts of microneedles and nanoparticles with specific and successful examples is missing. In this review, we have attempted to briefly analyse the challenges associated with nanomedicine itself, but crucially we provide an easy-to-navigate scheme of methods, suitable for characterisation and imaging the physico-chemical properties of the material matrix.
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Affiliation(s)
- Rachel E Sully
- Medway School of Pharmacy, Universities of Greenwich and Kent, Anson Building, Central Avenue, Chatham, ME4 4TB, UK.
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38
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Bondarenko O, Mortimer M, Kahru A, Feliu N, Javed I, Kakinen A, Lin S, Xia T, Song Y, Davis TP, Lynch I, Parak WJ, Leong DT, Ke PC, Chen C, Zhao Y. Nanotoxicology and Nanomedicine: The Yin and Yang of Nano-Bio Interactions for the New Decade. NANO TODAY 2021; 39:101184. [PMID: 36937379 PMCID: PMC10018814 DOI: 10.1016/j.nantod.2021.101184] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
Nanotoxicology and nanomedicine are two sub-disciplines of nanotechnology focusing on the phenomena, mechanisms, and engineering at the nano-bio interface. For the better part of the past three decades, these two disciplines have been largely developing independently of each other. Yet recent breakthroughs in microbiome research and the current COVID-19 pandemic demonstrate that holistic approaches are crucial for solving grand challenges in global health. Here we show the Yin and Yang relationship between the two fields by highlighting their shared goals of making safer nanomaterials, improved cellular and organism models, as well as advanced methodologies. We focus on the transferable knowledge between the two fields as nanotoxicological research is moving from pristine to functional nanomaterials, while inorganic nanomaterials - the main subjects of nanotoxicology - have become an emerging source for the development of nanomedicines. We call for a close partnership between the two fields in the new decade, to harness the full potential of nanotechnology for benefiting human health and environmental safety.
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Affiliation(s)
- Olesja Bondarenko
- Laboratory of Environmental Toxicology, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618 Tallinn, Estonia
- Institute of Biotechnology, HiLIFE, University of Helsinki, Viikinkaari 5d, 00790 Helsinki, Finland
| | - Monika Mortimer
- Institute of Environmental and Health Sciences, College of Quality and Safety Engineering, China Jiliang University, Hangzhou, Zhejiang 310018, China
| | - Anne Kahru
- Laboratory of Environmental Toxicology, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618 Tallinn, Estonia
- Estonian Academy of Sciences, Kohtu 6, 10130 Tallinn, Estonia
| | - Neus Feliu
- Fachbereich Physik und Chemie, Universität Hamburg, 22607 Hamburg, Germany
| | - Ibrahim Javed
- Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD 4072, Australia
| | - Aleksandr Kakinen
- Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD 4072, Australia
| | - Sijie Lin
- College of Environmental Science and Engineering, Biomedical Multidisciplinary Innovation Research Institute, Shanghai East Hospital, Tongji University, 1239 Siping Road, Shanghai 200092, China
| | - Tian Xia
- Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China
- Division of NanoMedicine, Department of Medicine, University of California Los Angeles (UCLA), 570 Westwood Plaza, CNSI 6511, Los Angeles, CA 90095, United States
| | - Yang Song
- Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China
- Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Rd, Beibei District, Chongqing, 400715, China
| | - Thomas P. Davis
- Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD 4072, Australia
- ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia
| | - Iseult Lynch
- School of Geography Earth and Environmental Sciences, University of Birmingham, Birmingham, B15 2TT, United Kingdom
| | - Wolfgang J. Parak
- Fachbereich Physik und Chemie, Universität Hamburg, 22607 Hamburg, Germany
- Department of Instrument Science and Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Jiao Tong University, 200240 Shanghai, China
| | - David Tai Leong
- Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore
| | - Pu Chun Ke
- ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia
- Zhongshan Hospital, Fudan University, 111 Yixueyuan Rd, Xuhui District, Shanghai, 200032, China
| | - Chunying Chen
- CAS Center for Excellence in Nanoscience and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China
| | - Yuliang Zhao
- CAS Center for Excellence in Nanoscience and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China
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39
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Advances in Functionalized Photosensitive Polymeric Nanocarriers. Polymers (Basel) 2021; 13:polym13152464. [PMID: 34372067 PMCID: PMC8348146 DOI: 10.3390/polym13152464] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 06/30/2021] [Accepted: 07/01/2021] [Indexed: 02/06/2023] Open
Abstract
The synthesis of light-responsive nanocarriers (LRNs) with a variety of surface functional groups and/or ligands has been intensively explored for space-temporal controlled cargo release. LRNs have been designed on demand for photodynamic-, photothermal-, chemo-, and radiotherapy, protected delivery of bioactive molecules, such as smart drug delivery systems and for theranostic duties. LRNs trigger the release of cargo by a light stimulus. The idea of modifying LRNs with different moieties and ligands search for site-specific cargo delivery imparting stealth effects and/or eliciting specific cellular interactions to improve the nanosystems’ safety and efficacy. This work reviews photoresponsive polymeric nanocarriers and photo-stimulation mechanisms, surface chemistry to link ligands and characterization of the resultant nanosystems. It summarizes the interesting biomedical applications of functionalized photo-controlled nanocarriers, highlighting the current challenges and opportunities of such high-performance photo-triggered delivery systems.
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40
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Eco-Interactions of Engineered Nanomaterials in the Marine Environment: Towards an Eco-Design Framework. NANOMATERIALS 2021; 11:nano11081903. [PMID: 34443734 PMCID: PMC8398366 DOI: 10.3390/nano11081903] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/14/2021] [Accepted: 07/22/2021] [Indexed: 12/23/2022]
Abstract
Marine nano-ecotoxicology has emerged with the purpose to assess the environmental risks associated with engineered nanomaterials (ENMs) among contaminants of emerging concerns entering the marine environment. ENMs’ massive production and integration in everyday life applications, associated with their peculiar physical chemical features, including high biological reactivity, have imposed a pressing need to shed light on risk for humans and the environment. Environmental safety assessment, known as ecosafety, has thus become mandatory with the perspective to develop a more holistic exposure scenario and understand biological effects. Here, we review the current knowledge on behavior and impact of ENMs which end up in the marine environment. A focus on titanium dioxide (n-TiO2) and silver nanoparticles (AgNPs), among metal-based ENMs massively used in commercial products, and polymeric NPs as polystyrene (PS), largely adopted as proxy for nanoplastics, is made. ENMs eco-interactions with chemical molecules including (bio)natural ones and anthropogenic pollutants, forming eco- and bio-coronas and link with their uptake and toxicity in marine organisms are discussed. An ecologically based design strategy (eco-design) is proposed to support the development of new ENMs, including those for environmental applications (e.g., nanoremediation), by balancing their effectiveness with no associated risk for marine organisms and humans.
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41
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Artificial Protein Coronas Enable Controlled Interaction with Corneal Epithelial Cells: New Opportunities for Ocular Drug Delivery. Pharmaceutics 2021; 13:pharmaceutics13060867. [PMID: 34204664 PMCID: PMC8231102 DOI: 10.3390/pharmaceutics13060867] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 06/02/2021] [Accepted: 06/03/2021] [Indexed: 11/16/2022] Open
Abstract
Topical administration is the most convenient route for ocular drug delivery, but only a minor fraction is retained in the precorneal pocket. To overcome this limitation, numerous drug delivery systems (DDS) have been developed. The protein corona (PC) is the layer of biomolecules (e.g., proteins, sugars, lipids, etc.) that forms around DDS in physiological environments by non-covalent interaction. The PC changes the DDS physical-chemical properties, providing them with a completely novel biological identity. The specific involvement of PC in ocular drug delivery has not been addressed so far. To fulfill this gap, here we explored the interaction between a library of four cationic liposome-DNA complexes (lipoplexes) and mucin (MUC), one of the main components of the tear film. We demonstrate that MUC binds to the lipoplex surface shifting both their size and surface charge and reducing their absorption by primary corneal epithelial cells. To surpass such restrictions, we coated lipoplexes with two different artificial PCs made of Fibronectin (FBN) and Val-Gly-Asp (VGA) tripeptide that are recognized by receptors expressed on the ocular surface. Both these functionalizations remarkedly boosted internalization in corneal epithelial cells with respect to pristine (i.e., uncoated) lipoplexes. This opens the gateway for the exploitation of artificial protein corona in targeted ocular delivery, which will significantly influence the development of novel nanomaterials.
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Imperlini E, Celia C, Cevenini A, Mandola A, Raia M, Fresta M, Orrù S, Di Marzio L, Salvatore F. Nano-bio interface between human plasma and niosomes with different formulations indicates protein corona patterns for nanoparticle cell targeting and uptake. NANOSCALE 2021; 13:5251-5269. [PMID: 33666624 DOI: 10.1039/d0nr07229j] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Unraveling the proteins interacting with nanoparticles (NPs) in biological fluids, such as blood, is pivotal to rationally design NPs for drug delivery. The protein corona (PrC), formed on the NP surface, represents an interface between biological components and NPs, dictating their pharmacokinetics and biodistribution. PrC composition depends on biological environments around NPs and on their intrinsic physicochemical properties. We generated different formulations of non-ionic surfactant/non-phospholipid vesicles, called niosomes (NIOs), using polysorbates which are biologically safe, cheap, non-toxic and scarcely immunogenic. PrC composition and relative protein abundance for all designed NIOs were evaluated ex vivo in human plasma (HP) by quantitative label-free proteomics. We studied the correlation of the relative protein abundance in the corona with cellular uptake of the PrC-NIOs in healthy and cancer human cell lines. Our results highlight the effects of polysorbates on nano-bio interactions to identify a protein pattern most properly aimed to drive the NIO targeting in vivo, and assess the best conditions of PrC-NIO NP uptake into the cells. This study dissected the biological identity in HP of polysorbate-NIOs, thus contributing to shorten their passage from preclinical to clinical studies and to lay the foundations for a personalized PrC.
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Affiliation(s)
| | - Christian Celia
- Dipartimento di Farmacia, Università di Chieti-Pescara "G. d'Annunzio", Chieti, Italy.
| | - Armando Cevenini
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Napoli, Italy. and CEINGE-Biotecnologie Avanzate S.c.a r.l., Napoli, Italy.
| | - Annalisa Mandola
- CEINGE-Biotecnologie Avanzate S.c.a r.l., Napoli, Italy. and Dipartimento di Scienze Motorie e del Benessere, Università "Parthenope", Napoli, Italy
| | - Maddalena Raia
- CEINGE-Biotecnologie Avanzate S.c.a r.l., Napoli, Italy.
| | - Massimo Fresta
- Dipartimento di Scienze della Salute, Università "Magna Graecia" di Catanzaro, Campus Universitario "S. Venuta", Catanzaro, Italy
| | - Stefania Orrù
- CEINGE-Biotecnologie Avanzate S.c.a r.l., Napoli, Italy. and Dipartimento di Scienze Motorie e del Benessere, Università "Parthenope", Napoli, Italy
| | - Luisa Di Marzio
- Dipartimento di Farmacia, Università di Chieti-Pescara "G. d'Annunzio", Chieti, Italy.
| | - Francesco Salvatore
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Napoli, Italy. and CEINGE-Biotecnologie Avanzate S.c.a r.l., Napoli, Italy.
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Attarde SS, Pandit SV. In Vivo Toxicity Profile of NN-32 and Nanogold Conjugated GNP-NN-32 from Indian Spectacled Cobra Venom. Curr Pharm Biotechnol 2021; 21:1479-1488. [PMID: 32427082 DOI: 10.2174/1389201021666200519101221] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 03/21/2020] [Accepted: 04/24/2020] [Indexed: 01/28/2023]
Abstract
BACKGROUND NN-32 toxin, which was obtained from Naja naja venom and showed cytotoxicity on cancer cell lines. As the toxicity of NN-32 is the main hurdle in the process of drug development; hence, we have conjugated NN-32 toxin with gold nanoparticles (GNP-NN-32) in order to decrease the toxicity of NN-32 without reducing its efficacy, GNP-NN-32 alleviated the toxicity of NN-32 in in vitro studies during the course of earlier studies. In continuation, we are evaluating in vivo toxicity profile of NN-32 and GNP-NN-32 in the present study. OBJECTIVE To study in vivo toxicity profile of NN-32 and nanogold conjugated GNP-NN-32 from Naja naja venom. MATERIALS AND METHODS We have carried out in vivo acute toxicity study to determine LD50 dose of GNP-NN-32, in vivo sub-chronic toxicity for 30 days, haematology, serum biochemical parameters and histopathology study on various mice tissues and in vitro cellular and tissue toxicity studies. RESULTS The LD50 dose of GNP-NN-32 was found to be 2.58 mg/kg (i.p.) in Swiss male albino mice. In vivo sub-chronic toxicity showed significantly reduced toxicity of GNP-NN-32 as compared to NN-32 alone. DISCUSSION In vitro cellular toxicity studies on human lymphocyte and mouse peritoneal macrophage showed significant inhibition of cells by NN-32 alone. CONCLUSION Conjugated GNP-NN-32 toxin showed less in vivo toxicity as compared to pure NN-32.
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Affiliation(s)
- Saurabh S Attarde
- Department of Zoology, Savitribai Phule Pune University, Pune, Maharashtra, India
| | - Sangeeta V Pandit
- Department of Zoology, Savitribai Phule Pune University, Pune, Maharashtra, India
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Dobrovolskaia MA, Bathe M. Opportunities and challenges for the clinical translation of structured DNA assemblies as gene therapeutic delivery and vaccine vectors. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2021; 13:e1657. [PMID: 32672007 PMCID: PMC7736207 DOI: 10.1002/wnan.1657] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 05/27/2020] [Accepted: 05/29/2020] [Indexed: 12/12/2022]
Abstract
Gene therapeutics including siRNAs, anti-sense oligos, messenger RNAs, and CRISPR ribonucleoprotein complexes offer unmet potential to treat over 7,000 known genetic diseases, as well as cancer, through targeted in vivo modulation of aberrant gene expression and immune cell activation. Compared with viral vectors, nonviral delivery vectors offer controlled immunogenicity and low manufacturing cost, yet suffer from limitations in toxicity, targeting, and transduction efficiency. Structured DNA assemblies fabricated using the principle of scaffolded DNA origami offer a new nonviral delivery vector with intrinsic, yet controllable immunostimulatory properties and virus-like spatial presentation of ligands and immunogens for cell-specific targeting, activation, and control over intracellular trafficking, in addition to low manufacturing cost. However, the relative utilities and limitations of these vectors must clearly be demonstrated in preclinical studies for their clinical potential to be realized. Here, we review the major capabilities, opportunities, and challenges we foresee in translating these next-generation delivery and vaccine vectors to the clinic. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
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Affiliation(s)
- Marina A. Dobrovolskaia
- Nanotechnology Characterization Laboratory, Cancer Research Technology ProgramFrederick National Laboratory for Cancer Research sponsored by National Cancer InstituteFrederickMaryland
| | - Mark Bathe
- Department of Biological EngineeringMassachusetts Institute of TechnologyCambridgeMassachusetts
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Aliyandi A, Zuhorn IS, Salvati A. Disentangling Biomolecular Corona Interactions With Cell Receptors and Implications for Targeting of Nanomedicines. Front Bioeng Biotechnol 2020; 8:599454. [PMID: 33363128 PMCID: PMC7758247 DOI: 10.3389/fbioe.2020.599454] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 11/17/2020] [Indexed: 12/12/2022] Open
Abstract
Nanoparticles are promising tools for nanomedicine in a wide array of therapeutic and diagnostic applications. Yet, despite the advances in the biomedical applications of nanomaterials, relatively few nanomedicines made it to the clinics. The formation of the biomolecular corona on the surface of nanoparticles has been known as one of the challenges toward successful targeting of nanomedicines. This adsorbed protein layer can mask targeting moieties and creates a new biological identity that critically affects the subsequent biological interactions of nanomedicines with cells. Extensive studies have been directed toward understanding the characteristics of this layer of biomolecules and its implications for nanomedicine outcomes at cell and organism levels, yet several aspects are still poorly understood. One aspect that still requires further insights is how the biomolecular corona interacts with and is “read” by the cellular machinery. Within this context, this review is focused on the current understanding of the interactions of the biomolecular corona with cell receptors. First, we address the importance and the role of receptors in the uptake of nanoparticles. Second, we discuss the recent advances and techniques in characterizing and identifying biomolecular corona-receptor interactions. Additionally, we present how we can exploit the knowledge of corona-cell receptor interactions to discover novel receptors for targeting of nanocarriers. Finally, we conclude this review with an outlook on possible future perspectives in the field. A better understanding of the first interactions of nanomaterials with cells, and -in particular -the receptors interacting with the biomolecular corona and involved in nanoparticle uptake, will help for the successful design of nanomedicines for targeted delivery.
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Affiliation(s)
- Aldy Aliyandi
- Department of Nanomedicine & Drug Targeting, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands
| | - Inge S Zuhorn
- Department of Biomedical Engineering, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
| | - Anna Salvati
- Department of Nanomedicine & Drug Targeting, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands
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Finbloom JA, Sousa F, Stevens MM, Desai TA. Engineering the drug carrier biointerface to overcome biological barriers to drug delivery. Adv Drug Deliv Rev 2020; 167:89-108. [PMID: 32535139 PMCID: PMC10822675 DOI: 10.1016/j.addr.2020.06.007] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 06/04/2020] [Accepted: 06/05/2020] [Indexed: 02/06/2023]
Abstract
Micro and nanoscale drug carriers must navigate through a plethora of dynamic biological systems prior to reaching their tissue or disease targets. The biological obstacles to drug delivery come in many forms and include tissue barriers, mucus and bacterial biofilm hydrogels, the immune system, and cellular uptake and intracellular trafficking. The biointerface of drug carriers influences how these carriers navigate and overcome biological barriers for successful drug delivery. In this review, we examine how key material design parameters lead to dynamic biointerfaces and improved drug delivery across biological barriers. We provide a brief overview of approaches used to engineer key physicochemical properties of drug carriers, such as morphology, surface chemistry, and topography, as well as the development of dynamic responsive materials for barrier navigation. We then discuss essential biological barriers and how biointerface engineering can enable drug carriers to better navigate and overcome these barriers to drug delivery.
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Affiliation(s)
- Joel A Finbloom
- Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA
| | - Flávia Sousa
- Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, United Kingdom
| | - Molly M Stevens
- Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, United Kingdom
| | - Tejal A Desai
- Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
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Bunea AI, Taboryski R. Recent Advances in Microswimmers for Biomedical Applications. MICROMACHINES 2020; 11:E1048. [PMID: 33261101 PMCID: PMC7760273 DOI: 10.3390/mi11121048] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 11/24/2020] [Accepted: 11/26/2020] [Indexed: 12/14/2022]
Abstract
Microswimmers are a rapidly developing research area attracting enormous attention because of their many potential applications with high societal value. A particularly promising target for cleverly engineered microswimmers is the field of biomedical applications, where many interesting examples have already been reported for e.g., cargo transport and drug delivery, artificial insemination, sensing, indirect manipulation of cells and other microscopic objects, imaging, and microsurgery. Pioneered only two decades ago, research studies on the use of microswimmers in biomedical applications are currently progressing at an incredibly fast pace. Given the recent nature of the research, there are currently no clinically approved microswimmer uses, and it is likely that several years will yet pass before any clinical uses can become a reality. Nevertheless, current research is laying the foundation for clinical translation, as more and more studies explore various strategies for developing biocompatible and biodegradable microswimmers fueled by in vivo-friendly means. The aim of this review is to provide a summary of the reported biomedical applications of microswimmers, with focus on the most recent advances. Finally, the main considerations and challenges for clinical translation and commercialization are discussed.
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Affiliation(s)
- Ada-Ioana Bunea
- National Centre for Nano Fabrication and Characterization (DTU Nanolab), Technical University of Denmark, Ørsted Plads 347, 2800 Lyngby, Denmark;
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Abstract
Nanomedicine is an interdisciplinary field of research, comprising science, engineering, and medicine. Many are the clinical applications of nanomedicine, such as molecular imaging, medical diagnostics, targeted therapy, and image-guided surgery. Despite major advances during the past 20 years, many efforts must be done to understand the complex behavior of nanoparticles (NPs) under physiological conditions, the kinetic and thermodynamic principles, involved in the rational design of NP. Once administrated in physiological environment, NPs interact with biomolecules and they are surrounded by protein corona (PC) or biocorona. PC can trigger an immune response, affecting NPs toxicity and targeting capacity. This review aims to provide a detailed description of biocorona and of parameters that are able to control PC formation and composition. Indeed, the review provides an overview about the role of PC in the modulation of both cytotoxicity and immune response as well as in the control of targeting capacity.
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Affiliation(s)
- Elisa Fasoli
- Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Milan, Italy
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Granz CL, Gorji A. Dental stem cells: The role of biomaterials and scaffolds in developing novel therapeutic strategies. World J Stem Cells 2020; 12:897-921. [PMID: 33033554 PMCID: PMC7524692 DOI: 10.4252/wjsc.v12.i9.897] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/05/2020] [Accepted: 08/16/2020] [Indexed: 02/06/2023] Open
Abstract
Dental stem cells (DSCs) are self-renewable cells that can be obtained easily from dental tissues, and are a desirable source of autologous stem cells. The use of DSCs for stem cell transplantation therapeutic approaches is attractive due to their simple isolation, high plasticity, immunomodulatory properties, and multipotential abilities. Using appropriate scaffolds loaded with favorable biomolecules, such as growth factors, and cytokines, can improve the proliferation, differentiation, migration, and functional capacity of DSCs and can optimize the cellular morphology to build tissue constructs for specific purposes. An enormous variety of scaffolds have been used for tissue engineering with DSCs. Of these, the scaffolds that particularly mimic tissue-specific micromilieu and loaded with biomolecules favorably regulate angiogenesis, cell-matrix interactions, degradation of extracellular matrix, organized matrix formation, and the mineralization abilities of DSCs in both in vitro and in vivo conditions. DSCs represent a promising cell source for tissue engineering, especially for tooth, bone, and neural tissue restoration. The purpose of the present review is to summarize the current developments in the major scaffolding approaches as crucial guidelines for tissue engineering using DSCs and compare their effects in tissue and organ regeneration.
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Affiliation(s)
- Cornelia Larissa Granz
- Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster 48149, Germany
| | - Ali Gorji
- Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster 48149, Germany
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50
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Francia V, Schiffelers RM, Cullis PR, Witzigmann D. The Biomolecular Corona of Lipid Nanoparticles for Gene Therapy. Bioconjug Chem 2020; 31:2046-2059. [PMID: 32786370 DOI: 10.1021/acs.bioconjchem.0c00366] [Citation(s) in RCA: 160] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Gene therapy holds great potential for treating almost any disease by gene silencing, protein expression, or gene correction. To efficiently deliver the nucleic acid payload to its target tissue, the genetic material needs to be combined with a delivery platform. Lipid nanoparticles (LNPs) have proven to be excellent delivery vectors for gene therapy and are increasingly entering into routine clinical practice. Over the past two decades, the optimization of LNP formulations for nucleic acid delivery has led to a well-established body of knowledge culminating in the first-ever RNA interference therapeutic using LNP technology, i.e., Onpattro, and many more in clinical development to deliver various nucleic acid payloads. Screening a lipid library in vivo for optimal gene silencing potency in hepatocytes resulted in the identification of the Onpattro formulation. Subsequent studies discovered that the key to Onpattro's liver tropism is its ability to form a specific "biomolecular corona". In fact, apolipoprotein E (ApoE), among other proteins, adsorbed to the LNP surface enables specific hepatocyte targeting. This proof-of-principle example demonstrates the use of the biomolecular corona for targeting specific receptors and cells, thereby opening up the road to rationally designing LNPs. To date, however, only a few studies have explored in detail the corona of LNPs, and how to efficiently modulate the corona remains poorly understood. In this review, we summarize recent discoveries about the biomolecular corona, expanding the knowledge gained with other nanoparticles to LNPs for nucleic acid delivery. In particular, we address how particle stability, biodistribution, and targeting of LNPs can be influenced by the biological environment. Onpattro is used as a case study to describe both the successful development of an LNP formulation for gene therapy and the key influence of the biological environment. Moreover, we outline the techniques available to isolate and analyze the corona of LNPs, and we highlight their advantages and drawbacks. Finally, we discuss possible implications of the biomolecular corona for LNP delivery and we examine the potential of exploiting the corona as a targeting strategy beyond the liver to develop next-generation gene therapies.
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Affiliation(s)
- Valentina Francia
- Department of Biochemistry and Molecular Biology, University of British Columbia, V6T 1Z3, Vancouver, British Columbia, Canada.,Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, 3584 CX, Utrecht, Netherlands
| | - Raymond M Schiffelers
- Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, 3584 CX, Utrecht, Netherlands
| | - Pieter R Cullis
- Department of Biochemistry and Molecular Biology, University of British Columbia, V6T 1Z3, Vancouver, British Columbia, Canada.,NanoMedicines Innovation Network (NMIN), University of British Columbia, V6T 1Z3, Vancouver, British Columbia, Canada
| | - Dominik Witzigmann
- Department of Biochemistry and Molecular Biology, University of British Columbia, V6T 1Z3, Vancouver, British Columbia, Canada.,NanoMedicines Innovation Network (NMIN), University of British Columbia, V6T 1Z3, Vancouver, British Columbia, Canada
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