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Almeida MB, Galdiano CMR, Silva Benvenuto FSRD, Carrilho E, Brazaca LC. Strategies Employed to Design Biocompatible Metal Nanoparticles for Medical Science and Biotechnology Applications. ACS APPLIED MATERIALS & INTERFACES 2024; 16:67054-67072. [PMID: 38688024 DOI: 10.1021/acsami.4c00838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/02/2024]
Abstract
The applicability of nanomaterials has evolved in biomedical domains thanks to advances in biocompatibility strategies and the mitigation of cytotoxic effects, allowing diagnostics, imaging, and therapeutic approaches. The application of nanoparticles (NP), particularly metal nanoparticles (mNPs), such as gold (Au) and silver (Ag), includes inherent challenges related to the material characteristics, surface modification, and bioconjugation techniques. By tailoring the surface properties through appropriate coating with biocompatible molecules or functionalization with active biomolecules, researchers can reach a harmonious interaction with biological systems or samples (mostly fluids or tissues). Thus, this review highlights the mechanisms associated with the obtention of biocompatible mNP and presents a comprehensive overview of methods that facilitate safe and efficient production. Therefore, we consider this review to be a valuable resource for all researchers navigating this dynamic field.
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Affiliation(s)
- Mariana Bortholazzi Almeida
- Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, São Paulo 13566-590, Brazil
- Instituto Nacional de Ciência e Tecnologia de Bioanalítica-INCTBio, Campinas, São Paulo 13083-970, Brazil
| | | | - Filipe Sampaio Reis da Silva Benvenuto
- Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, São Paulo 13566-590, Brazil
- Instituto Nacional de Ciência e Tecnologia de Bioanalítica-INCTBio, Campinas, São Paulo 13083-970, Brazil
| | - Emanuel Carrilho
- Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, São Paulo 13566-590, Brazil
- Instituto Nacional de Ciência e Tecnologia de Bioanalítica-INCTBio, Campinas, São Paulo 13083-970, Brazil
| | - Laís Canniatti Brazaca
- Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, São Paulo 13566-590, Brazil
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Ibraheem HH, Queen BK, Al-Sabti MD, Issa AA, Al-Majedy YK, Jabir MS, Sulaiman GM, Hasoon BA, Eshaq MM, Jawad KH, Jawad SF, Fawzi HA, Shuaib M, Najm MAA, Swelum AA. Insights into the pharmaceutical properties and in silico study of novel hydrazone derivatives. Sci Rep 2024; 14:29912. [PMID: 39622881 PMCID: PMC11612229 DOI: 10.1038/s41598-024-81555-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 11/27/2024] [Indexed: 12/06/2024] Open
Abstract
It has been established that the Hydrazone derivatives have important pharmacological effects. In the first step, hydrazine (NH2NH2) reacts with a compound containing a carbonyl group (C = O) in the presence of ethanol and heat, leading to the formation of hydrazone compound (H1). The second step is the formation of the Schiff base (H2) by the reaction of compound (H1) with indole, ethanol, and acetic acid, which contain a double bond (C = N). In the third step, the (H1) reacts with thiophene, ethanol, and acetic acid to form a compound (H3) containing multiple bonds between the indole and thiophene rings. The synthetic test compounds underwent characterization using TLC, IR, 1 H - NMR, and ¹3C NMR spectral examinations. Both compounds, H2 and H3, exhibit antioxidant activity at different concentrations (from 12.5 to 100 µgmL- 1), where the effect increases gradually with the increase in concentration. The compounds (H2 and H3) exhibited an apparent inhibitory effect on the growth of Staphylococcus aureus, Escherichia coli, and Candida albicans. Calculations have been performed for DFT, molecular docking, molecular dynamics simulations, and the ADMET protocol, and they are essential for describing the interaction and stability. In hydrazone derivatives, groups like amine, hydroxy, thiophene, and indole form hydrogen bonds and electrostatic interactions with amino acids such as arginine, lysine, glutamic acid, and aspartic acid. These interactions are crucial to evaluating the compound's stability and its potential to inhibit enzyme activity. The results indicate that the compound shows strong binding and stability at the active site, making it a promising candidate for further studies as an anti-colon cancer agent.
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Affiliation(s)
- Hiba H Ibraheem
- Department of Applied Sciences, University of Technology, Baghdad, Iraq
| | - Batool K Queen
- Department of Applied Sciences, University of Technology, Baghdad, Iraq
| | | | - Ali A Issa
- Department of Applied Sciences, University of Technology, Baghdad, Iraq
| | | | - Majid S Jabir
- Department of Applied Sciences, University of Technology, Baghdad, Iraq.
| | - Ghassan M Sulaiman
- Department of Applied Sciences, University of Technology, Baghdad, Iraq.
| | - Buthenia A Hasoon
- Department of Applied Sciences, University of Technology, Baghdad, Iraq
| | - Merriam M Eshaq
- Department of Biomedical Engineering, University of Technology, Baghdad, Iraq
| | - Kareem H Jawad
- Department Laser and Optoelectronics Engineering, University of Technology, Baghdad, Iraq
| | - Sabrean F Jawad
- Department of Pharmacy, Al-Mustaqbal University, Hillah, 51001, Iraq
| | - Hayder A Fawzi
- Department of Pharmacy, AL Mustafa University, Baghdad, Iraq
| | - Muhammad Shuaib
- Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China
| | - Mazin A A Najm
- Department of Pharmacy, Mazaya University College, Nasiriyah, Iraq
| | - Ayman A Swelum
- Department of Animal Production, College of Food and Agriculture Sciences, King Saud University, Riyadh, 11451, Saudi Arabia.
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Rangam N, Sudagar A, Koronkiewicz R, Borowicz P, Tóth J, Kövér L, Michałowska D, Roszko M, Pilz M, Kwapiszewska K, Lesiak-Orłowska B. Surface and composition effects on the biphasic cytotoxicity of nanocomposites synthesized using leaf extracts. Int J Biol Macromol 2024; 276:133723. [PMID: 38981556 DOI: 10.1016/j.ijbiomac.2024.133723] [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: 11/30/2023] [Revised: 07/04/2024] [Accepted: 07/05/2024] [Indexed: 07/11/2024]
Abstract
The Malus sylvestris L. (LE1), Pinus sylvestris L. (LE2), and Sorbus aucuparia L. (LE3) leaves` extracts were used for the synthesis of silver (Ag) nanocomposites containing different amounts of silver chloride (AgCl), silver metal (Agmet), and silver phosphate (Ag3PO4). These nanocomposites were capped with the organic functional groups in the leaf extract. Notably, the nanocomposites caused biphasic cytotoxic response on cells; first attributed to the inhibition of cell growth and second to cell death. The nanocomposites were biocompatible with normal embryonic kidney (HEK293) cells in the cytotoxic range for cancer cells. [25(±1) °C synthesis] nanocomposites exhibited the highest cytotoxicity towards HeLa (lethal concentration- LC50 value of 11.4 μg mL-1) and A549 (LC50 value of 14.7 μg mL-1) after 24-h incubation and its efficiency was shown also for the more resistant MCF-7 and MDA-MB-231, however, their respective LC50 values were larger. For the HeLa cell line, this designed nanocomposite exhibited an LC50 value similar to the effective concentration (EC50) value of Cisplatin and about 3 times larger than Doxorubicin. nanocomposite contained Ag3PO4 in the composite and P on the surface, higher AgCl content, smaller crystallite size of all nanoparticle phases, and carbon-rich oxygen-deficient surface compared to all other nanocomposites.
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Affiliation(s)
- Neha Rangam
- Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
| | - Alcina Sudagar
- Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland; Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO 63130, USA.
| | - Roksana Koronkiewicz
- The Cardinal Stefan Wyszyński University in Warsaw, Dewajtis 5, 01-815 Warsaw, Poland
| | - Paweł Borowicz
- Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
| | - József Tóth
- HUN-REN Institute for Nuclear Research, BemTér 18/c, H-4026 Debrecen, Hungary
| | - László Kövér
- HUN-REN Institute for Nuclear Research, BemTér 18/c, H-4026 Debrecen, Hungary
| | - Dorota Michałowska
- Institute of Agriculture and Food Biotechnology-State Research Institute, ul. Rakowiecka 36, 02-532 Warsaw, Poland
| | - Marek Roszko
- Institute of Agriculture and Food Biotechnology-State Research Institute, ul. Rakowiecka 36, 02-532 Warsaw, Poland
| | - Marta Pilz
- Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
| | - Karina Kwapiszewska
- Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
| | - Beata Lesiak-Orłowska
- Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
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Radzikowski D, Kalińska A, Kot M, Jaworski S, Wierzbicki M, Gołębiewski M. In Vitro Evaluation of the Antimicrobial Properties of Nanoparticles as New Agents Used in Teat Sealants for Mastitis Prevention in Dry Cows. Biomedicines 2023; 11:2291. [PMID: 37626787 PMCID: PMC10452312 DOI: 10.3390/biomedicines11082291] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 08/07/2023] [Accepted: 08/16/2023] [Indexed: 08/27/2023] Open
Abstract
Mastitis prevention and treatment in dry cows are complex issues with limited solutions. The most common is intramammary antibiotic treatment. However, the effectiveness of this treatment varies among countries and even within herds in the same region. Therefore, it is necessary to develop new strategies for dry cow therapy. Metal nanoparticles (NPs), which have strong biocidal properties for treating diseases caused by bacteria, fungi, and algae, are increasingly used to reduce antibiotic use. In this study, AuNPs, CuNPs, AgNPs, PtNPs, NP-FeCs, and their triple complexes were used at different concentrations to evaluate their practical use in treating cows during their dry period. The nanoparticles were in hydrocolloid form and were added separately to form a mixture with beeswax, a mixture with oil, or a mixture based on vegetable glycerin and propylene glycol. The NPs' concentrations were 0.5, 1, 2, and 5 ppm. Gram-positive and Gram-negative bacteria, and fungi isolated from cows diagnosed with mastitis were used to determine pathogen viability. The results indicated that AuNPs, CuNPs, AgNPs, and their complexes show biocidal properties against mastitis pathogens. AgNPs at 5 ppm had the strongest biocidal properties and reduced Streptococcus agalactiae's survival rate by 50%; however, the nanoparticle complexes showed poor synergism. The strongest biocidal properties of NPs in wax and in glycerin mixed with glycol were shown against Escherichia coli. Additionally, low nanoparticle concentrations showed no cytotoxicity for BME-UV1 bovine cells, suggesting that these mixtures might be used for further in vivo testing.
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Affiliation(s)
- Daniel Radzikowski
- Animal Breeding Department, Warsaw University of Life Sciences, 02-786 Warszawa, Poland; (A.K.); (M.K.)
| | - Aleksandra Kalińska
- Animal Breeding Department, Warsaw University of Life Sciences, 02-786 Warszawa, Poland; (A.K.); (M.K.)
| | - Magdalena Kot
- Animal Breeding Department, Warsaw University of Life Sciences, 02-786 Warszawa, Poland; (A.K.); (M.K.)
| | - Sławomir Jaworski
- Department of Nanobiotechnology, Warsaw University of Life Sciences, 02-786 Warszawa, Poland (M.W.)
| | - Mateusz Wierzbicki
- Department of Nanobiotechnology, Warsaw University of Life Sciences, 02-786 Warszawa, Poland (M.W.)
| | - Marcin Gołębiewski
- Animal Breeding Department, Warsaw University of Life Sciences, 02-786 Warszawa, Poland; (A.K.); (M.K.)
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Busch M, Brouwer H, Aalderink G, Bredeck G, Kämpfer AAM, Schins RPF, Bouwmeester H. Investigating nanoplastics toxicity using advanced stem cell-based intestinal and lung in vitro models. FRONTIERS IN TOXICOLOGY 2023; 5:1112212. [PMID: 36777263 PMCID: PMC9911716 DOI: 10.3389/ftox.2023.1112212] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 01/17/2023] [Indexed: 01/28/2023] Open
Abstract
Plastic particles in the nanometer range-called nanoplastics-are environmental contaminants with growing public health concern. As plastic particles are present in water, soil, air and food, human exposure via intestine and lung is unavoidable, but possible health effects are still to be elucidated. To better understand the Mode of Action of plastic particles, it is key to use experimental models that best reflect human physiology. Novel assessment methods like advanced cell models and several alternative approaches are currently used and developed in the scientific community. So far, the use of cancer cell line-based models is the standard approach regarding in vitro nanotoxicology. However, among the many advantages of the use of cancer cell lines, there are also disadvantages that might favor other approaches. In this review, we compare cell line-based models with stem cell-based in vitro models of the human intestine and lung. In the context of nanoplastics research, we highlight the advantages that come with the use of stem cells. Further, the specific challenges of testing nanoplastics in vitro are discussed. Although the use of stem cell-based models can be demanding, we conclude that, depending on the research question, stem cells in combination with advanced exposure strategies might be a more suitable approach than cancer cell lines when it comes to toxicological investigation of nanoplastics.
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Affiliation(s)
- Mathias Busch
- Division of Toxicology, Wageningen University and Research, Wageningen, Netherlands
| | - Hugo Brouwer
- Division of Toxicology, Wageningen University and Research, Wageningen, Netherlands
| | - Germaine Aalderink
- Division of Toxicology, Wageningen University and Research, Wageningen, Netherlands
| | - Gerrit Bredeck
- IUF—Leibniz-Research Institute for Environmental Medicine, Duesseldorf, Germany
| | | | - Roel P. F. Schins
- IUF—Leibniz-Research Institute for Environmental Medicine, Duesseldorf, Germany
| | - Hans Bouwmeester
- Division of Toxicology, Wageningen University and Research, Wageningen, Netherlands,*Correspondence: Hans Bouwmeester,
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New Insights into the Cellular Toxicity of Carbon Quantum Dots to Escherichia coli. Antioxidants (Basel) 2022; 11:antiox11122475. [PMID: 36552683 PMCID: PMC9774514 DOI: 10.3390/antiox11122475] [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: 11/05/2022] [Revised: 12/08/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022] Open
Abstract
In this study, the cytotoxicity and toxic mechanism of carbon quantum dots (CQDs) to E. coli were evaluated in vitro. The synthetic CQDs were extremely small in size (~2.08 nm) and displayed strong fluorescence. The results demonstrated that CQDs showed good biocompatibility with E. coli within a short culture time. However, when the exposure time exceeded 24 h, the toxicity of CQDs became apparent, and the contents of reactive oxygen species, lactate dehydrogenase, and the crystal violet absorption rate increased significantly. To further explore the cytotoxic mechanism, approaches including confocal laser scanning microscopy, scanning electron microscopy, and biological transmission electron microscopy combined with zeta potential tests, osmotic pressure measurement, and comet assays were performed. On the one hand, the CQDs altered the surface charges of cells and induced lipid peroxidation by adhesion on the surface of E. coli, leading to an increase in the permeability of the cell wall. On the other hand, when the concentration of CQDs reached 200 µg/mL, the osmotic pressure of the extracellular environment was significantly reduced. These are the main factors that lead to cell edema and death. Finally, the comet assays confirmed that CQDs could induce DNA damage, which could inhibit the proliferation of E. coli.
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Camassa LMA, Elje E, Mariussen E, Longhin EM, Dusinska M, Zienolddiny-Narui S, Rundén-Pran E. Advanced Respiratory Models for Hazard Assessment of Nanomaterials—Performance of Mono-, Co- and Tricultures. NANOMATERIALS 2022; 12:nano12152609. [PMID: 35957046 PMCID: PMC9370172 DOI: 10.3390/nano12152609] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/23/2022] [Accepted: 07/26/2022] [Indexed: 12/02/2022]
Abstract
Advanced in vitro models are needed to support next-generation risk assessment (NGRA), moving from hazard assessment based mainly on animal studies to the application of new alternative methods (NAMs). Advanced models must be tested for hazard assessment of nanomaterials (NMs). The aim of this study was to perform an interlaboratory trial across two laboratories to test the robustness of and optimize a 3D lung model of human epithelial A549 cells cultivated at the air–liquid interface (ALI). Potential change in sensitivity in hazard identification when adding complexity, going from monocultures to co- and tricultures, was tested by including human endothelial cells EA.hy926 and differentiated monocytes dTHP-1. All models were exposed to NM-300K in an aerosol exposure system (VITROCELL® cloud-chamber). Cyto- and genotoxicity were measured by AlamarBlue and comet assay. Cellular uptake was investigated with transmission electron microscopy. The models were characterized by confocal microscopy and barrier function tested. We demonstrated that this advanced lung model is applicable for hazard assessment of NMs. The results point to a change in sensitivity of the model by adding complexity and to the importance of detailed protocols for robustness and reproducibility of advanced in vitro models.
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Affiliation(s)
| | - Elisabeth Elje
- NILU—Norwegian Institute for Air Research, 2027 Kjeller, Norway; (E.E.); (E.M.); (E.M.L.); (M.D.)
- Institute of Basic Medical Sciences, Department of Molecular Medicine, University of Oslo, 0372 Oslo, Norway
| | - Espen Mariussen
- NILU—Norwegian Institute for Air Research, 2027 Kjeller, Norway; (E.E.); (E.M.); (E.M.L.); (M.D.)
- Norwegian Institute of Public Health, FHI, 0456 Oslo, Norway
| | - Eleonora Marta Longhin
- NILU—Norwegian Institute for Air Research, 2027 Kjeller, Norway; (E.E.); (E.M.); (E.M.L.); (M.D.)
| | - Maria Dusinska
- NILU—Norwegian Institute for Air Research, 2027 Kjeller, Norway; (E.E.); (E.M.); (E.M.L.); (M.D.)
| | - Shan Zienolddiny-Narui
- National Institute of Occupational Health in Norway, 0033 Oslo, Norway;
- Correspondence: (S.Z.-N.); (E.R.-P.); Tel.: +47-2319-5284 (S.Z.-N.); +47-6389-8237 (E.R.-P.)
| | - Elise Rundén-Pran
- NILU—Norwegian Institute for Air Research, 2027 Kjeller, Norway; (E.E.); (E.M.); (E.M.L.); (M.D.)
- Correspondence: (S.Z.-N.); (E.R.-P.); Tel.: +47-2319-5284 (S.Z.-N.); +47-6389-8237 (E.R.-P.)
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Naik LS, Ramana Devi CV. Phyto-fabricated silver nanoparticles inducing microbial cell death via reactive oxygen species-mediated membrane damage. IET Nanobiotechnol 2021; 15:492-504. [PMID: 34694754 PMCID: PMC8675829 DOI: 10.1049/nbt2.12036] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 07/12/2020] [Accepted: 11/18/2020] [Indexed: 01/15/2023] Open
Abstract
Eco‐friendly synthesis of the silver nanoparticles (AgNPs) has a number of advantages like simplicity, biocompatibility, low toxicity in nature over their physical and chemical methods. In the present study, the authors report biosynthesized AgNPs using the root extract of the perennial plant ‘Spiny gourd’ (Momordica dioica) and investigated their anti‐bacterial application with mechanistic approaches. Different biophysical techniques such as UV‐Vis spectroscopy, FTIR, XRD, TEM, SAED, and DLS were employed for AgNPs characterization. The synthesized AgNPs were polydispersed, crystalline in nature, with anionic surface (−22.3 mV), spherical in shape with an average size of 13.2 nm. In addition, the AgNPs were stable in room temperature and in different biological buffers. The anti‐bacterial activities of AgNPs were studied with respect to the pathogens such as Bacillus subtilis, Staphylococcus aureus (Gram‐positive), Pseudomonas aeruginosa, Escherichia coli, Klebsiella planticola (Gram‐negative), and Candida albicans. Also, mechanistic studies of AgNPs such as protein leakage assay, nucleic acid leakage assay, ATP leakage assay, ROS accumulation, determination of biofilm degrading activity, measurement of potassium, showing that the synthesized AgNPs are capable of containing a potential application in the antimicrobial therapeutic agents and the pharmaceutical industry.
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Affiliation(s)
- L Srinivas Naik
- Department of Biochemistry, University College of Science, Osmania University, Hyderabad, India
| | - Ch Venkata Ramana Devi
- Department of Biochemistry, University College of Science, Osmania University, Hyderabad, India
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9
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Amina M, Al Musayeib N, Al-Hamoud G, Al-Dbass A, El-Ansary A, Ali M. Prospective of biosynthesized L.satiVum oil/PEG/Ag-MgO bionanocomposite film for its antibacterial and anticancer potential. Saudi J Biol Sci 2021; 28:5971-5985. [PMID: 34588914 PMCID: PMC8459159 DOI: 10.1016/j.sjbs.2021.06.052] [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: 05/19/2021] [Revised: 06/19/2021] [Accepted: 06/20/2021] [Indexed: 11/24/2022] Open
Abstract
A substantial interest has been manifested in utilizing oil/metal oxide hybrid bionanocomposite, especially organic/ inorganic to design different biomedical applications. The present study reports the synthesis, characterization, antibacterial and anticancer properties of biogenic silver nanoparticles (AgNPs) and L.satiVum oil/PEG/Ag-MgO bionanocomposite. The fabricated AgNPs and L.sativum oil/PEG/Ag-MgO bionanocomposite were characterized by employing different spectroscopic (UV, FTIR, XRD) and microscopic (TEM, SEM) techniques. The particle size analysis showed that the mean size of 16.32 nm for AgNPS and 13.45 nm L.satiVum oil/PEG/Ag-MgO, indicating the excellent dispersion of Ag-MgO nanoparticles in the PEG- L.satiVum oil matrix. The antimicrobial activity of AgNPs and polymeric bionanocomposite was investigated against two pathogenic bacteria. The highest antibacterial effect was observed for bionanocomposite towards Gram-positive Staphylococcus aureus (27 mm) and Gram-negative Escherichia coli (25 mm) at 40 µg/well. The bionanocomposite completely vanished the bacterial growth (100%) at 80 µgmL-1 concentrations. Moreover, the AgNPs and polymeric bionanocomposite was evaluated for anticancer activity against human cervical cancer cells (HeLa cells) at different doses (50, 250, 500, and 1000 µgmL-1). The results showed polymeric bionanocomposite was stronger in inducing the HeLa cancer cell death than AgNPs. Overall, the fabricated L.satiVum oil/PEG/Ag-MgO bionanocomposite serve as a potential antimicrobial and anticancer agent and could be used in the development of novel drugs and health care products in near future.
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Affiliation(s)
- M. Amina
- Department of Pharmacognosy, Pharmacy College, King Saud University, Riyadh 11451, Saudi Arabia
| | - N.M. Al Musayeib
- Department of Pharmacognosy, Pharmacy College, King Saud University, Riyadh 11451, Saudi Arabia
| | - G.A. Al-Hamoud
- Department of Pharmacognosy, Pharmacy College, King Saud University, Riyadh 11451, Saudi Arabia
| | - A. Al-Dbass
- Biochemistry Department, College of Sciences, King Saud University, Riyadh, Saudi Arabia
| | - A. El-Ansary
- Central Laboratory, Female Centre for Scientific and Medical Studies, King Saud University, Riyadh, Saudi Arabia
| | - M.A. Ali
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
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10
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Precipitation at Room Temperature as a Fast and Versatile Method for Calcium Phosphate/TiO 2 Nanocomposites Synthesis. NANOMATERIALS 2021; 11:nano11061523. [PMID: 34207588 PMCID: PMC8230063 DOI: 10.3390/nano11061523] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 05/24/2021] [Accepted: 06/07/2021] [Indexed: 11/16/2022]
Abstract
The constantly growing need for advanced bone regeneration materials has motivated the development of calcium phosphates (CaPs) composites with a different metal or metal-oxide nanomaterials and their economical and environmentally friendly production. Here, two procedures for the synthesis of CaPs composites with TiO2 nanoplates (TiNPl) and nanowires (TiNWs) were tested, with the immersion of TiO2 nanomaterials (TiNMs) in corrected simulated body fluid (c-SBF) and precipitation of CaP in the presence of TiNMs. The materials obtained were analyzed by powder X-ray diffraction, spectroscopic and microscopic techniques, Brunauer–Emmett–Teller surface area analysis, thermogravimetric analysis, dynamic and electrophoretic light scattering, and their hemocompatibility and ability to induce reactive oxygen species were evaluated. After 28 days of immersion in c-SBF, no significant CaP coating was formed on TiNMs. However, the composites with calcium-deficient apatite (CaDHA) were obtained after one hour in the spontaneous precipitation system. In the absence of TiNMs, CaDHA was also formed, indicating that control of the CaP phase formed can be accomplished by fine-tuning conditions in the precipitation system. Although the morphology and size of crystalline domains of CaDHA obtained on the different nanomaterials differed, no significant difference was detected in their local structure. Composites showed low reactive oxygen species (ROS) production and did not induce hemolysis. The results obtained indicate that precipitation is a suitable and fast method for the preparation of CaPs/TiNMs nanocomposites which shows great potential for biomedical applications.
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El-Kaliuoby MI, Amer M, Shehata N. Enhancement of Nano-Biopolymer Antibacterial Activity by Pulsed Electric Fields. Polymers (Basel) 2021; 13:1869. [PMID: 34200040 PMCID: PMC8200249 DOI: 10.3390/polym13111869] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 05/20/2021] [Accepted: 05/30/2021] [Indexed: 11/17/2022] Open
Abstract
Chronic wounds are commonly colonized with bacteria in a way that prevents full healing process and capacity for repair. Nano-chitosan, a biodegradable and nontoxic biopolymer, has shown bacteriostatic activity against a wide spectrum of bacteria. Effectively, pulsed electromagnetic fields are shown to have both wound healing enhancement and antibacterial activity. This work aimed to combine the use of nano-chitosan and exposure to a pulsed electric field to overcome two common types of infectious bacteria, namely P. aeruginosa and S. aureus. Here, bacteria growing rate, growth kinetics and cell cytotoxicity (levels of lactate dehydrogenase, protein leakage and nucleic acid leakage) were investigated. Our findings confirmed the maximum antibacterial synergistic combination of nano-chitosan and exposure against P. aeruginosa than using each one alone. It is presumed that the exposure has influenced bacteria membrane charge distribution in a manner that allowed more chitosan to anchor the surface and enter inside the cell. Significantly, cell cytotoxicity substantiates high enzymatic levels as a result of cell membrane disintegration. In conclusion, exposure to pulsed electromagnetic fields has a synergistic antibacterial effect against S. aureus and P. aeruginosa with maximum inhibitory effect for the last one. Extensive work should be done to evaluate the combination against different bacteria types to get general conclusive results. The ability of using pulsed electromagnetic fields as a wound healing accelerator and antibacterial cofactor has been proved, but in vivo experimental work in the future to verify the use of such a new combination against infectious wounds and to determine optimum treatment conditions is a must.
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Affiliation(s)
| | - Motaz Amer
- Basic and Applied Science Institute, College of Engineering Arab Academy for Science, Technology and Maritime Transports, Alexandria 21544, Egypt;
| | - Nader Shehata
- The Bradley Department of Electrical and Computer Engineering, Virginia Tech, Blacksburg, VA 24061, USA
- Department of Engineering Mathematics and Physics, Faculty of Engineering, Alexandria University, Alexandria 21544, Egypt
- Kuwait College of Science and Technology, Doha Area, 7th Ring Road, Safat 13133, Kuwait
- Utah Science Technology and Research (USTAR) Bio-Innovation Center, Utah State University, Logan, UT 84341, USA
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12
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Matter MT, Doppegieter M, Gogos A, Keevend K, Ren Q, Herrmann IK. Inorganic nanohybrids combat antibiotic-resistant bacteria hiding within human macrophages. NANOSCALE 2021; 13:8224-8234. [PMID: 33885075 PMCID: PMC8101700 DOI: 10.1039/d0nr08285f] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 03/08/2021] [Indexed: 05/02/2023]
Abstract
Bacterial infections are one of the main health concerns humanity faces today and bacterial resistances and protection mechanisms are set to aggravate the issue in the coming years. An increasing number of bacterial strains evades antibiotic treatment by hiding inside cells. Conventional antimicrobial agents are unable to penetrate or be retained in the infected mammalian cells. Recent approaches to overcome these limitations have focused on load-carrier systems, requiring a triggered discharge leading to complex release kinetics. The unison of potent antimicrobial activity with high mammalian cell compatibility is a prerequisite for intracellular activity, which is not well-met by otherwise well-established inorganic systems, such as silver-based nanoparticles. In this work, load and carrier are combined into one functional inorganic nanoparticle system, which unites antimicrobial activity with mammalian cell compatibility. These multicomponent nanohybrids based on cerium oxide are produced in one step, yet unite complex materials. The nanoparticles form suprastructures of similar size and surface charge as bacteria, therefore facilitating the uptake into the same subcellular compartments, where they unleash their antibacterial effect. Such intrinsically antibacterial nanohybrids significantly reduce bacterial survival inside macrophages without harming the latter. Furthermore, blocking of nanoparticle endocytosis and subcellular electron microscopy elucidate the mechanism of action. Taken together, this work presents the first demonstration of antibacterial activity of ceria-based nanoparticles inside of mammalian cells and offers a route to straightforward and robust intracellular antibacterial agents that do not depend on payload delivery or biological constituents.
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Affiliation(s)
- Martin T. Matter
- Laboratory for Particles-Biology Interactions, Department of Materials Meet Life, Swiss Federal Laboratories for Materials Science and Technology (Empa)Lerchenfeldstrasse 59014 St GallenSwitzerland+41 (0)58 765 71 53
- Nanoparticle Systems Engineering Laboratory, Institute of Process Engineering, Department of Mechanical and Process Engineering, ETH ZurichSonneggstrasse 38092 ZurichSwitzerland
| | - Meagan Doppegieter
- Laboratory for Particles-Biology Interactions, Department of Materials Meet Life, Swiss Federal Laboratories for Materials Science and Technology (Empa)Lerchenfeldstrasse 59014 St GallenSwitzerland+41 (0)58 765 71 53
| | - Alexander Gogos
- Laboratory for Particles-Biology Interactions, Department of Materials Meet Life, Swiss Federal Laboratories for Materials Science and Technology (Empa)Lerchenfeldstrasse 59014 St GallenSwitzerland+41 (0)58 765 71 53
- Nanoparticle Systems Engineering Laboratory, Institute of Process Engineering, Department of Mechanical and Process Engineering, ETH ZurichSonneggstrasse 38092 ZurichSwitzerland
| | - Kerda Keevend
- Laboratory for Particles-Biology Interactions, Department of Materials Meet Life, Swiss Federal Laboratories for Materials Science and Technology (Empa)Lerchenfeldstrasse 59014 St GallenSwitzerland+41 (0)58 765 71 53
- Nanoparticle Systems Engineering Laboratory, Institute of Process Engineering, Department of Mechanical and Process Engineering, ETH ZurichSonneggstrasse 38092 ZurichSwitzerland
| | - Qun Ren
- Laboratory for Biointerfaces, Department of Materials Meet Life, Swiss Federal Laboratories for Materials Science and Technology (Empa)Lerchenfeldstrasse 59014 St. GallenSwitzerland
| | - Inge K. Herrmann
- Laboratory for Particles-Biology Interactions, Department of Materials Meet Life, Swiss Federal Laboratories for Materials Science and Technology (Empa)Lerchenfeldstrasse 59014 St GallenSwitzerland+41 (0)58 765 71 53
- Nanoparticle Systems Engineering Laboratory, Institute of Process Engineering, Department of Mechanical and Process Engineering, ETH ZurichSonneggstrasse 38092 ZurichSwitzerland
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13
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Ozulumba T, Ingavle G, Gogotsi Y, Sandeman S. Moderating cellular inflammation using 2-dimensional titanium carbide MXene and graphene variants. Biomater Sci 2021; 9:1805-1815. [PMID: 33443511 DOI: 10.1039/d0bm01953d] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The effective control of microbial and metabolically derived biological toxins which negatively impact physical health remains a key challenge for the 21st century. 2-Dimensional graphene and MXene nanomaterials are relatively new additions to the field of biomedical materials with superior external surface areas suited to adsorptive remediation of biological toxins. However, relatively little is known about their physiological interactions with biological systems and, to date, no comparative biological studies have been done. This study compares titanium carbide MXene (Ti3C2Tx) in multilayered and delaminated forms with graphene variants to assess the impact of variable physical properties on cellular inflammatory response to endotoxin stimulus. No significant impact on cell metabolism or induction of inflammatory pathways leading to cell death was observed. No significant increase in markers of blood cell activation and haemolysis occurred. Whilst graphene nanoplatelets (GNP), graphene oxide (GO) and Ti3C2Tx showed insignificant antibacterial activity towards Escherichia coli, silver nanoparticle-modified GO (GO-Ag) induced bacterial cell death and at a lower dose than silver nanoparticles. All nanomaterials significantly reduced bacterial endotoxin induced THP-1 monocyte IL-8, IL-6 and TNF-α cytokine production by >99%, >99% and >80% respectively, compared to control groups. This study suggests the utility of these nanomaterials as adsorbents in blood contacting medical device applications for removal of inflammatory cytokines linked to poor outcome in patients with life-threatening infection.
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Affiliation(s)
- Tochukwu Ozulumba
- School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, UK. and Department of Chemistry, University of Virginia, Charlottesville, VA 22904, USA
| | - Ganesh Ingavle
- School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, UK. and Symbiosis Centre for Stem Cell Research, Symbiosis International University, Lavale, Pune-412115, India
| | - Yury Gogotsi
- Department of Material Science and Engineering, and A. J. Drexel Nanomaterials Institute, Drexel University, Philadelphia, PA 19104, USA
| | - Susan Sandeman
- School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, UK.
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14
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Thiagarajan V, Alex SA, Seenivasan R, Chandrasekaran N, Mukherjee A. Interactive effects of micro/nanoplastics and nanomaterials/pharmaceuticals: Their ecotoxicological consequences in the aquatic systems. AQUATIC TOXICOLOGY (AMSTERDAM, NETHERLANDS) 2021; 232:105747. [PMID: 33493974 DOI: 10.1016/j.aquatox.2021.105747] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 12/29/2020] [Accepted: 01/10/2021] [Indexed: 06/12/2023]
Abstract
Micro/nanoplastics are ubiquitous in the environment and cause pollution of the aquatic ecosystem, in particular, which is a serious concern worldwide. Micro/nanoplastics can act as a vector for multiple co-contaminants that co-exist in the aquatic environment. Apart from micro/nanoplastics, nanomaterials and pharmaceuticals are other emerging contaminants that can also raise severe problems. Thus, in this review, the physicochemical interactions occurring between micro/nanoplastics and nanomaterials and pharmaceuticals and the factors (chemical and environmental) affecting the sorption efficiency of nanomaterials and pharmaceuticals have been addressed. Furthermore, the influence of micro/nanoplastics on the bioavailability and toxic effects of nanomaterials and pharmaceuticals on both freshwater and marine species has been highlighted. Additional focus has also been given to study the mechanism of toxicity of the micro/nanoplastics-nanomaterials and pharmaceuticals complex on the different species of different trophic levels. Finally, this review addresses the knowledge gaps and provides insights into the future research strategies to better understand the interactive mechanisms between the binary contaminants and also the toxicity mechanisms of micro/nanoplastics and nanomaterials and pharmaceuticals.
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Affiliation(s)
- Vignesh Thiagarajan
- Centre for Nanobiotechnology, Vellore Institute of Technology (VIT), Vellore, India
| | - Sruthi Ann Alex
- Centre for Nano Science and Technology, Anna University, Chennai, India
| | - R Seenivasan
- Centre for Nanobiotechnology, Vellore Institute of Technology (VIT), Vellore, India
| | - N Chandrasekaran
- Centre for Nanobiotechnology, Vellore Institute of Technology (VIT), Vellore, India
| | - Amitava Mukherjee
- Centre for Nanobiotechnology, Vellore Institute of Technology (VIT), Vellore, India.
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15
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Antibacterial Synergism of Electrospun Nanofiber Mats Functioned with Silver Nanoparticles and Pulsed Electromagnetic Waves. Polymers (Basel) 2021; 13:polym13020277. [PMID: 33467752 PMCID: PMC7829770 DOI: 10.3390/polym13020277] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Revised: 01/08/2021] [Accepted: 01/08/2021] [Indexed: 12/23/2022] Open
Abstract
The over-reliance on antibiotics and their enormous misuse has led to warnings of a future without effective medicines and so, the need for alternatives to antibiotics has become a must. Non-traditional antibacterial treatment was performed by using an aray of nanocomposites synergised with exposure to electromagnetic waves. In this manuscript, electrospun poly(vinyl alcohol) (PVA) nanofiber mats embedded with silver nanoparticles (Ag NPs) were synthesized. The nanocomposites were characterized by Transmission Electron Microscope (TEM), Scanning Electron Microscope (SEM), Current-Voltage (I-V) curves, and Thermogravimetric analysis (TGA) along with analysis of antibacterial impact against E. coli and S. aureus bacteria, studied by bacterial growing analysis, growth kinetics, and cellular cytotoxicity. The results indicated a spherical grain shape of silver of average size 20 nm and nanofibers' mean diameter of less than 100 nm. The nanocomposite mats showed good exposure to bacteria and the ability to sustain release of silver for a relatively long time. Moreover, the applied electromagnetic waves (EMWs) were shown to be a synergistic co-factor in killing bacteria even at low concentrations of Ag NPs. This caused pronounced alterations of the bacterial preserved packing of the cell membrane. Thereby, the treatment with nanocomposite mats under EM wave exposure elucidated maximum inhibition for both bacterial strains. It was concluded that the functioning of nanofiber with silver nanoparticles and exposure to electromagnetic waves improved the antibacterial impact compared to each one alone.
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16
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Do VQ, Seo YS, Park JM, Yu J, Duong MTH, Nakai J, Kim SK, Ahn HC, Lee MY. A mixture of chloromethylisothiazolinone and methylisothiazolinone impairs rat vascular smooth muscle by depleting thiols and thereby elevating cytosolic Zn 2+ and generating reactive oxygen species. Arch Toxicol 2020; 95:541-556. [PMID: 33074372 DOI: 10.1007/s00204-020-02930-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Accepted: 10/08/2020] [Indexed: 12/26/2022]
Abstract
Chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) are biocidal preservatives and the active ingredients in Kathon CG, which contains ca. 1.5% mixture of CMIT and MIT at a ratio of 3:1 (CMIT/MIT). CMIT/MIT was misused as humidifier disinfectant products, which caused serious health problems in Korea. Here, the vascular effects of CMIT/MIT were investigated to evaluate claims of putative cardiovascular toxicity observed in humidifier disinfectant users. CMIT/MIT did not affect the basal tension of the rat thoracic aorta up to 2.5 μg/mL in myograph experiments. Instead, pretreatment with CMIT/MIT impaired phenylephrine- or 5-hydroxytryptamine-induced vasoconstriction in a range of 0.5-2.5 μg/mL, which was largely irreversible and not recovered by washing out the CMIT/MIT. Similarly, the application of CMIT/MIT to pre-contracted aorta caused a gradual loss of tension. In primary cultured vascular smooth muscle cells (VSMCs), CMIT/MIT caused thiol depletion, which in turn led to cytosolic Zn2+ elevation and reactive oxygen species (ROS) formation. CMIT/MIT-induced shrinkage, detachment, and lysis of VSMCs depending on the concentration and the treatment time. All events induced by CMIT/MIT were prevented by a thiol donor N-acetylcysteine (NAC). Cytolysis could be inhibited by a Zn2+ chelator TPEN and a superoxide scavenger TEMPOL, whereas they did not affect shrinkage and detachment. In accordance with these results, CMIT/MIT-exposed aortas exhibited dissociation and collapse of tissue in histology analysis. Taken together, CMIT/MIT causes functional impairment and tissue damage to blood vessels by depleting thiol and thereby elevating cytosolic Zn2+ and generating ROS. Therefore, exposure to CMIT/MIT in consumer products may be a risk factor for cardiovascular disorders.
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Affiliation(s)
- Van Quan Do
- College of Pharmacy, Integrated Research Institute for Drug Development, and BK21 FOUR team, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea
| | - Yoon-Seok Seo
- College of Pharmacy, Integrated Research Institute for Drug Development, and BK21 FOUR team, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea
| | - Jung-Min Park
- College of Pharmacy, Integrated Research Institute for Drug Development, and BK21 FOUR team, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea
| | - Jieun Yu
- College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea
| | - Men Thi Hoai Duong
- College of Pharmacy, Integrated Research Institute for Drug Development, and BK21 FOUR team, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea
| | - Junichi Nakai
- Graduate School of Dentistry, Tohoku University, Miyagi, 980-8575, Japan
| | - Sang-Kyum Kim
- College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea
| | - Hee-Chul Ahn
- College of Pharmacy, Integrated Research Institute for Drug Development, and BK21 FOUR team, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea
| | - Moo-Yeol Lee
- College of Pharmacy, Integrated Research Institute for Drug Development, and BK21 FOUR team, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea.
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17
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Andraos C, Yu IJ, Gulumian M. Interference: A Much-Neglected Aspect in High-Throughput Screening of Nanoparticles. Int J Toxicol 2020; 39:397-421. [PMID: 32672081 DOI: 10.1177/1091581820938335] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Despite several studies addressing nanoparticle (NP) interference with conventional toxicity assay systems, it appears that researchers still rely heavily on these assays, particularly for high-throughput screening (HTS) applications in order to generate "big" data for predictive toxicity approaches. Moreover, researchers often overlook investigating the different types of interference mechanisms as the type is evidently dependent on the type of assay system implemented. The approaches implemented in the literature appear to be not adequate as it often addresses only one type of interference mechanism with the exclusion of others. For example, interference of NPs that have entered cells would require intracellular assessment of their interference with fluorescent dyes, which has so far been neglected. The present study investigated the mechanisms of interference of gold NPs and silver NPs in assay systems implemented in HTS including optical interference as well as adsorption or catalysis. The conventional assays selected cover all optical read-out systems, that is, absorbance (XTT toxicity assay), fluorescence (CytoTox-ONE Homogeneous membrane integrity assay), and luminescence (CellTiter Glo luminescent assay). Furthermore, this study demonstrated NP quenching of fluorescent dyes also used in HTS (2',7'-dichlorofluorescein, propidium iodide, and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzamidazolocarbocyanin iodide). To conclude, NP interference is, as such, not a novel concept, however, ignoring this aspect in HTS may jeopardize attempts in predictive toxicology. It should be mandatory to report the assessment of all mechanisms of interference within HTS, as well as to confirm results with label-free methodologies to ensure reliable big data generation for predictive toxicology.
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Affiliation(s)
- Charlene Andraos
- Toxicology Department, 71899National Institute for Occupational Health, Johannesburg, South Africa
| | - Il Je Yu
- HCTm CO, LTD, Majang-myeon, Icheon, South Korea
| | - Mary Gulumian
- Toxicology Department, 71899National Institute for Occupational Health, Johannesburg, South Africa.,Haematology and Molecular Medicine Department, University of the Witwatersrand, Johannesburg, South Africa
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18
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Milić M, Vuković B, Barbir R, Pem B, Milić M, Šerić V, Frőhlich E, Vinković Vrček I. Effect of differently coated silver nanoparticles on hemostasis. Platelets 2020; 32:651-661. [PMID: 32668997 DOI: 10.1080/09537104.2020.1792432] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
With the emergence of nano-enabled medical devices (MDs) for the use in human medicine, ensuring their safety becomes of crucial importance. Hemocompatibility is one of the major criteria for approval of all MDs in contact with blood (e.g. vascular grafts, stents, or valves). Silver nanoparticles (AgNPs) are among the most used nanomaterials for MDs due to their biocidal activity; however, detailed knowledge on their hemostatic effects is still lacking.This study aimed to evaluate comprehensively AgNPs effects on hemostasis in human blood by exploiting combination of affordable and clinically relevant techniques.Differently stabilized AgNPs were prepared using sodium bis(2-ethylhexyl)sulphosuccinate (AOT), polyvinylpyrrolidone (PVP), poly-L-lysine (PLL), and bovine serum albumin (BSA) as coating agents. They were tested for hemolytic activity, induction of platelet aggregation, plasmatic coagulation, thrombin generation, and hemostasis in whole blood.All AgNPs were found to cause dose-dependent hemolysis. The BSA-, AOT-, and PVP-coated AgNPs delayed plasmatic coagulation, while only PLL-AgNPs inhibited plasmatic coagulation, induced platelet activation, and interfered with hemostasis by delaying clotting time and decreasing clot firmness in whole blood.Obtained results demonstrate that a combination of different techniques should be used for reliable assessment of AgNPs hemostatic effects highlighting the need for a standardized approach in sampling and experimental protocols.
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Affiliation(s)
- Marija Milić
- Department of Clinical Laboratory Diagnostics, Osijek University Hospital, Osijek, Croatia.,Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Barbara Vuković
- Department of Clinical Laboratory Diagnostics, Osijek University Hospital, Osijek, Croatia.,Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Rinea Barbir
- Institute for Medical Research and Occupational Health, Zagreb, Croatia
| | - Barbara Pem
- Institute for Medical Research and Occupational Health, Zagreb, Croatia
| | - Mirta Milić
- Institute for Medical Research and Occupational Health, Zagreb, Croatia
| | - Vatroslav Šerić
- Department of Clinical Laboratory Diagnostics, Osijek University Hospital, Osijek, Croatia.,Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
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19
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Zhang F, Aquino GV, Bruce ED. A quantitative and non-invasive method for nanoparticle translocation and toxicity evaluation in a human airway barrier model. MethodsX 2020; 7:100869. [PMID: 32382518 PMCID: PMC7199013 DOI: 10.1016/j.mex.2020.100869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Accepted: 03/11/2020] [Indexed: 11/10/2022] Open
Abstract
Human exposure to environmental nanoparticles (NPs) may result in systemic distribution and accumulation of NPs. Depending on exposure conditions and their physiochemical properties, NPs could cross biological barriers and reach vital organs. This method describes an analytical technique that quantifies the nanoparticles’ translocation through a sample human airway barrier. Silver nanoparticles (AgNPs) were used as the example nanoparticles due to their common use in nanotechnology. The analytical method introduced in this study allows mass measurements of both cellular uptake and translocation of AgNPs through the modeled barrier. Additionally, cytotoxicity was evaluated using a convenient assay to investigate adverse effects from AgNPs treatment. The assay measures cellular injury from each layer in the barrier independently. The assay does not engage cells physically for chemical reaction, therefore it is non-destructive to the model, and the model can be used for other purposes subsequently. To conclude, this study provides researchers with measurable tools for evaluating the translocation, cellular trafficking, uptake and toxic effects of metallic nanoparticles in the in vitro barrier format.
Quantitative evaluation of nanoparticles translocation through human airway barrier Non-invasive and quantifiable toxicity evaluation for co-culture models
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Affiliation(s)
- Fan Zhang
- Department of Environmental Science, Baylor University, One Bear Place #97266, Waco, 76798-7266 TX, United States
| | - Grace V Aquino
- Department of Environmental Science, Baylor University, One Bear Place #97266, Waco, 76798-7266 TX, United States
| | - Erica D Bruce
- Department of Environmental Science, Baylor University, One Bear Place #97266, Waco, 76798-7266 TX, United States
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20
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Gu Q, Cuevas E, Ali SF, Paule MG, Krauthamer V, Jones Y, Zhang Y. An Alternative In Vitro Method for Examining Nanoparticle-Induced Cytotoxicity. Int J Toxicol 2019; 38:385-394. [PMID: 31234669 DOI: 10.1177/1091581819859267] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Conventional in vitro assays are often used as initial screens to identify potential toxic effects of nanoparticles (NPs). However, many NPs have shown interference with conventional in vitro assays, resulting in either false-positive or -negative outcomes. Here, we report an alternative method for the in vitro assessment of NP-induced cytotoxicity utilizing Fluoro-Jade C (FJ-C). To provide proof of concept and initial validation data, Ag-NPs and Au-NPs were tested in 3 different cell cultures including rat brain microvessel endothelial cells, mouse neural stem cells, and the human SH-SY5Y cell line. Conventional 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and lactate dehydrogenase (LDH) assays were run in parallel with the new method and served as references. The results demonstrate for the first time that FJ-C labeling can be a useful tool for assessing NP-induced cytotoxicity in vitro. Using these approaches, it was also demonstrated that removal of Ag-NPs-while keeping the Ag-ions that were released from the Ag-NPs in culture media-abolished the measured cytotoxicity, indicating that Ag-NPs rather than Ag-ions in solution contributed to the observed cytotoxic effects. Further, co-treatment of Ag-NPs with N-acetyl cysteine (NAC) prevented the observed cytotoxicity, suggesting a protective role of NAC in Ag-NP-induced cytotoxicity. Thus, this alternative in vitro assay is well suited for identify potential cytotoxicity associated with exposure to NPs.
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Affiliation(s)
- Qiang Gu
- Division of Neurotoxicology, National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, USA
| | - Elvis Cuevas
- Division of Neurotoxicology, National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, USA
| | - Syed F Ali
- Division of Neurotoxicology, National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, USA
| | - Merle G Paule
- Division of Neurotoxicology, National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, USA
| | - Victor Krauthamer
- Division of Biomedical Physics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, FDA, Jefferson, AR, USA
| | - Yvonne Jones
- Nanotechnology Core Facility, Office of Scientific Coordination, NCTR, FDA, Jefferson, AR, USA
| | - Yongbin Zhang
- Nanotechnology Core Facility, Office of Scientific Coordination, NCTR, FDA, Jefferson, AR, USA
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21
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Do VQ, Park KH, Park JM, Lee MY. Comparative In Vitro Toxicity Study of Docetaxel and Nanoxel, a Docetaxel-Loaded Micellar Formulation Using Cultured and Blood Cells. Toxicol Res 2019; 35:201-207. [PMID: 31015902 PMCID: PMC6467357 DOI: 10.5487/tr.2019.35.2.201] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Revised: 09/18/2018] [Accepted: 10/04/2018] [Indexed: 12/20/2022] Open
Abstract
Nanoxel-PMTM (Nanoxel) is a docetaxel-loaded methoxy-poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA). This newly developed and marketed nanoformulation exhibits an improved pharmacokinetic profile, efficacy, and safety. Although the safety of Nanoxel to docetaxel as well as its bioequivalence must be clinically confirmed, all biological activities have not been examined in in vitro or in vivo studies. Here, the toxicity in a cultured cell system and the effects on blood cells were tested with Nanoxel and docetaxel. The in vitro cytotoxicity of Nanoxel was found to be comparable to or slightly lower than that of docetaxel depending on the concentrations tested or the cell types. Neither docetaxel nor Nanoxel induced erythrocytes hemolysis and produced reactive oxygen species up to 100 μM. However, Nanoxel was able to enhance the aggregatory response of platelets to collagen, whereas docetaxel attenuated such aggregation in a range of 50–100 μM, while thrombin-induced aggregation was not affected by either of them. Docetaxel or Nanoxel did not alter basal level of Ca2+ and 5-hydroxytryptamine-evoked Ca2+ transient in vascular smooth muscle cells. These results suggest that the mPEG-PDLLA micellar formulation alters the toxicological properties of docetaxel, and that extra cautions are needed when evaluating the safety of nanomedicine.
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Affiliation(s)
- Van Quan Do
- College of Pharmacy, Dongguk University, Goyang, Korea
| | | | - Jung-Min Park
- College of Pharmacy, Dongguk University, Goyang, Korea
| | - Moo-Yeol Lee
- College of Pharmacy, Dongguk University, Goyang, Korea
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22
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Silver and Copper Nanoparticles-An Alternative in Future Mastitis Treatment and Prevention? Int J Mol Sci 2019; 20:ijms20071672. [PMID: 30987188 PMCID: PMC6480535 DOI: 10.3390/ijms20071672] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 03/30/2019] [Accepted: 04/01/2019] [Indexed: 12/13/2022] Open
Abstract
Nowadays, mastitis is one of the biggest problems in breeding dairy cattle. Treatment of this disease with conventional antibiotics is ineffective because many pathogens are resistant. Researchers have therefore been forced to look for new solutions, and metal nanoparticles (NPs) have been found to be the most appropriate agents. This study uses commercially available silver (AgNPs) and copper (CuNPs) nanoparticles and synthetized silver–copper nanoparticles (AgCuNPs) to evaluate the effect of these NPs on human and bovine mammary cells. The effect of AgNPs, CuNPs, and AgCuNPs on pathogen species commonly involved in udder inflammation (e.g., Staphylococcus aureus and Escherichia coli) was also established. The results show that commercially available NPs were of good quality and did not have a toxic effect on mammary gland tissue. AgNPs, CuNPs, and AgCuNPs also influenced or decreased the viability of pathogens. Therefore, the presented data suggest that metal NPs could be used in mastitis prevention and treatment in the future. However, the presented preliminary results require further in vivo analysis.
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23
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Fizeșan I, Cambier S, Moschini E, Chary A, Nelissen I, Ziebel J, Audinot JN, Wirtz T, Kruszewski M, Pop A, Kiss B, Serchi T, Loghin F, Gutleb AC. In vitro exposure of a 3D-tetraculture representative for the alveolar barrier at the air-liquid interface to silver particles and nanowires. Part Fibre Toxicol 2019; 16:14. [PMID: 30940208 PMCID: PMC6444883 DOI: 10.1186/s12989-019-0297-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 03/06/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The present study aimed to evaluate the potential differences in the biological effects of two types of spherical silver particles of 20 and 200 nm (Ag20 and Ag200), and of PVP-coated silver nanowires (AgNWs) with a diameter of 50 nm and length up to 50 μm, using a complex 3D model representative for the alveolar barrier cultured at air-liquid interface (ALI). The alveolar model was exposed to 0.05, 0.5 and 5 μg/cm2 of test compounds at ALI using a state-of-the-art exposure system (Vitrocell™Cloud System). Endpoints related to the oxidative stress induction, anti-oxidant defence mechanisms, pro-inflammatory responses and cellular death were selected to evaluate the biocompatibility of silver particles and nanowires (AgNMs) and to further ascribe particular biological effects to the different morphologic properties between the three types of AgNMs evaluated. RESULTS Significant cytotoxic effect was observed for all three types of AgNMs at the highest tested doses. The increased mRNA levels of the pro-apoptotic gene CASP7 suggests that apoptosis may occur after exposure to AgNWs. All three types of AgNMs increased the mRNA level of the anti-oxidant enzyme HMOX-1 and of the metal-binding anti-oxidant metallothioneins (MTs), with AgNWs being the most potent inducer. Even though all types of AgNMs induced the nuclear translocation of NF-kB, only AgNWs increased the mRNA level of pro-inflammatory mediators. The pro-inflammatory response elicited by AgNWs was further confirmed by the increased secretion of the 10 evaluated interleukins. CONCLUSION In the current study, we demonstrated that the direct exposure of a complex tetra-culture alveolar model to different types of AgNMs at ALI induces shape- and size-specific biological responses. From the three AgNMs tested, AgNWs were the most potent in inducing biological alterations. Starting from 50 ng/cm2, a dose representative for an acute exposure in a high exposure occupational setting, AgNWs induced prominent changes indicative for a pro-inflammatory response. Even though the acute responses towards a dose representative for a full-lifetime exposure were also evaluated, chronic exposure scenarios at low dose are still unquestionably needed to reveal the human health impact of AgNMs during realistic conditions.
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Affiliation(s)
- Ionel Fizeșan
- Toxicology Department, Faculty of Pharmacy, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Sébastien Cambier
- Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg
| | - Elisa Moschini
- Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg
| | - Aline Chary
- Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg
| | - Inge Nelissen
- Health Unit, Flemish Institute for Technological Research (VITO NV), Mol, Belgium
| | - Johanna Ziebel
- Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg
| | - Jean-Nicolas Audinot
- Material Research and Technology (MRT) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg
| | - Tom Wirtz
- Material Research and Technology (MRT) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg
| | - Marcin Kruszewski
- Faculty of Medicine, University of Information Technology and Management in Rzeszow, Sucharskiego 2, Rzeszow, Poland
- Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, Warszawa, Poland
| | - Anca Pop
- Toxicology Department, Faculty of Pharmacy, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Béla Kiss
- Toxicology Department, Faculty of Pharmacy, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Tommaso Serchi
- Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg
| | - Felicia Loghin
- Toxicology Department, Faculty of Pharmacy, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Arno C. Gutleb
- Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg
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Pem B, González-Mancebo D, Moros M, Ocaña M, Becerro AI, Pavičić I, Selmani A, Babič M, Horák D, Vinković Vrček I. Biocompatibility assessment of up-and down-converting nanoparticles: implications of interferences with in vitro assays. Methods Appl Fluoresc 2018; 7:014001. [DOI: 10.1088/2050-6120/aae9c8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Oxidative stress mediated cytotoxicity of tin (IV) oxide (SnO 2) nanoparticles in human breast cancer (MCF-7) cells. Colloids Surf B Biointerfaces 2018; 172:152-160. [PMID: 30172199 DOI: 10.1016/j.colsurfb.2018.08.040] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Revised: 08/12/2018] [Accepted: 08/18/2018] [Indexed: 01/15/2023]
Abstract
Due to unique optical and electronic properties tin oxide nanoparticles (SnO2 NPs) have shown potential for various applications including solar cell, catalyst, and biomedicine. However, there is limited information concerning the interaction of SnO2 NPs with human cells. In this study, we explored the potential mechanisms of cytotoxicity of SnO2 NPs in human breast cancer (MCF-7) cells. Results demonstrated that SnO2 NPs induce cell viability reduction, lactate dehydrogenase leakage, rounded cell morphology, cell cycle arrest and low mitochondrial membrane potential in dose- and time-dependent manner. SnO2 NPs were also found to provoke oxidative stress evident by generation of reactive oxygen species (ROS), hydrogen peroxide (H2O2) and lipid peroxidation, while depletion of glutathione (GSH) level and lower activity of several antioxidant enzymes. Remarkably, we observed that ROS generation, GSH depletion, and cytotoxicity induced by SnO2 NPs were effectively abrogated by antioxidant N-acetylcycteine. Our data have shown that SnO2 NPs induce toxicity in MCF-7 cells via oxidative stress. This study warrants further research to explore the genotoxicity of SnO2 NPs in different types of cancer cells.
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Gioria S, Caputo F, Urbán P, Maguire CM, Bremer-Hoffmann S, Prina-Mello A, Calzolai L, Mehn D. Are existing standard methods suitable for the evaluation of nanomedicines: some case studies. Nanomedicine (Lond) 2018; 13:539-554. [PMID: 29381129 DOI: 10.2217/nnm-2017-0338] [Citation(s) in RCA: 91] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
The use of nanotechnology in medical products has been demonstrated at laboratory scale, and many resulting nanomedicines are in the translational phase toward clinical applications, with global market trends indicating strong growth of the sector in the coming years. The translation of nanomedicines toward the clinic and subsequent commercialization may require the development of new or adaptation of existing standards to ensure the quality, safety and efficacy of such products. This work addresses some identified needs, and illustrates the shortcomings of currently used standardized methods when applied to medical-nanoparticles to assess particle size, drug loading, drug release and in vitro safety. Alternative physicochemical, and in vitro toxicology methods, with the potential to qualify as future standards supporting the evaluation of nanomedicine are provided.
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Affiliation(s)
- Sabrina Gioria
- European Commission, Joint Research Center (JRC), Directorate for Health, Consumers & Reference Materials, Via Enrico Fermi 2749, I-21027 Ispra, VA, Italy
| | - Fanny Caputo
- Univ. Grenoble Alpes, F38000 Grenoble, France.,CEA, LETI, Minatec Campus, F-38054 Grenoble, France
| | - Patricia Urbán
- European Commission, Joint Research Center (JRC), Directorate for Health, Consumers & Reference Materials, Via Enrico Fermi 2749, I-21027 Ispra, VA, Italy
| | - Ciarán Manus Maguire
- Laboratory for Biological Characterization of Advanced Materials (LBCAM), Department of Clinical Medicine, Trinity Translational Medicine Institute (TTMI), School of Medicine, Trinity College Dublin, Dublin 8, Ireland.,AMBER Center & CRANN Institute, Trinity College Dublin, Dublin 2, Ireland
| | - Susanne Bremer-Hoffmann
- European Commission, Joint Research Center (JRC), Directorate for Health, Consumers & Reference Materials, Via Enrico Fermi 2749, I-21027 Ispra, VA, Italy
| | - Adriele Prina-Mello
- Laboratory for Biological Characterization of Advanced Materials (LBCAM), Department of Clinical Medicine, Trinity Translational Medicine Institute (TTMI), School of Medicine, Trinity College Dublin, Dublin 8, Ireland.,AMBER Center & CRANN Institute, Trinity College Dublin, Dublin 2, Ireland
| | - Luigi Calzolai
- European Commission, Joint Research Center (JRC), Directorate for Health, Consumers & Reference Materials, Via Enrico Fermi 2749, I-21027 Ispra, VA, Italy
| | - Dora Mehn
- European Commission, Joint Research Center (JRC), Directorate for Health, Consumers & Reference Materials, Via Enrico Fermi 2749, I-21027 Ispra, VA, Italy
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Panzarini E, Mariano S, Vergallo C, Carata E, Fimia GM, Mura F, Rossi M, Vergaro V, Ciccarella G, Corazzari M, Dini L. Glucose capped silver nanoparticles induce cell cycle arrest in HeLa cells. Toxicol In Vitro 2017; 41:64-74. [PMID: 28223142 DOI: 10.1016/j.tiv.2017.02.014] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 02/16/2017] [Accepted: 02/17/2017] [Indexed: 01/25/2023]
Abstract
This study aims to determine the interaction (uptake and biological effects on cell viability and cell cycle progression) of glucose capped silver nanoparticles (AgNPs-G) on human epithelioid cervix carcinoma (HeLa) cells, in relation to amount, 2×103 or 2×104 NPs/cell, and exposure time, up to 48h. The spherical and well dispersed AgNPs (30±5nm) were obtained by using glucose as reducing agent in a green synthesis method that ensures to stabilize AgNPs avoiding cytotoxic soluble silver ions Ag+ release. HeLa cells take up abundantly and rapidly AgNPs-G resulting toxic to cells in amount and incubation time dependent manner. HeLa cells were arrested at S and G2/M phases of the cell cycle and subG1 population increased when incubated with 2×104 AgNPs-G/cell. Mitotic index decreased accordingly. The dissolution experiments demonstrated that the observed effects were due only to AgNPs-G since glucose capping prevents Ag+ release. The AgNPs-G influence on HeLa cells viability and cell cycle progression suggest that AgNPs-G, alone or in combination with chemotherapeutics, may be exploited for the development of novel antiproliferative treatment in cancer therapy. However, the possible influence of the cell cycle on cellular uptake of AgNPs-G and the mechanism of AgNPs entry in cells need further investigation.
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Affiliation(s)
- Elisa Panzarini
- Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy.
| | - Stefania Mariano
- Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy.
| | - Cristian Vergallo
- Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy.
| | - Elisabetta Carata
- Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy.
| | - Gian Maria Fimia
- Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy.
| | - Francesco Mura
- Department of Base and Applied Science to Engineering, Sapienza University of Rome, Rome, Italy.
| | - Marco Rossi
- Department of Base and Applied Science to Engineering, Sapienza University of Rome, Rome, Italy.
| | - Viviana Vergaro
- Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy
| | - Giuseppe Ciccarella
- Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy; Institute of Nanotechnology - CNR (CNR-NANOTEC) Via Monteroni, 73100 Lecce, Italy
| | - Marco Corazzari
- Department of Biology, University of Rome Tor Vergata, Rome, Italy.
| | - Luciana Dini
- Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Lecce, Italy; CNR Nanotec, Lecce, Italy.
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Chang KH, Park JM, Lee CH, Kim B, Choi KC, Choi SJ, Lee K, Lee MY. NADPH oxidase (NOX) 1 mediates cigarette smoke-induced superoxide generation in rat vascular smooth muscle cells. Toxicol In Vitro 2017; 38:49-58. [PMID: 27816504 DOI: 10.1016/j.tiv.2016.10.013] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Revised: 08/08/2016] [Accepted: 10/31/2016] [Indexed: 11/18/2022]
Abstract
Smoking is a well-established risk factor for cardiovascular diseases. Oxidative stress is one of the common etiological factors, and NADPH oxidase (NOX) has been suggested as a potential mediator of oxidative stress. In this study, cigarette smoke (CS)-induced superoxide production was characterized in vascular smooth muscle cells (VSMC). CS was prepared in forms of cigarette smoke extract (CSE) and total particulate matter (TPM). Several molecular probes for reactive oxygen species were trialed, and dihydroethidium (DHE) and WST-1 were chosen for superoxide detection considering the autofluorescence, light absorbance, and peroxidase inhibitory activity of CS. Both CSE and TPM generated superoxide in a VSMC culture system by stimulating cells to produce superoxide and by directly producing superoxide in the aqueous solution. NOX, specifically NOX1 was found to be an important cellular source of superoxide through experiments with the NOX inhibitors diphenyleneiodonium (DPI) and VAS2870 as well as isoform-specific NOX knockdown. NOX inhibitors and the superoxide dismutase mimetic TEMPOL reduced the cytotoxicity of CSE, thus suggesting the contribution of NOX1-derived superoxide to cytotoxicity. Since NOX1 is known to mediate diverse pathological processes in the vascular system, NOX1 may be a critical effector of cardiovascular toxicity caused by smoking.
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MESH Headings
- Animals
- Aorta, Thoracic
- Male
- Muscle, Smooth, Vascular
- Myocytes, Smooth Muscle/drug effects
- Myocytes, Smooth Muscle/metabolism
- NADH, NADPH Oxidoreductases/genetics
- NADH, NADPH Oxidoreductases/metabolism
- NADPH Oxidase 1
- NADPH Oxidase 4
- NADPH Oxidases/genetics
- Particulate Matter/toxicity
- RNA, Messenger/metabolism
- RNA, Small Interfering/genetics
- Rats, Sprague-Dawley
- Smoke/adverse effects
- Superoxides/metabolism
- Nicotiana
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Affiliation(s)
- Kyung-Hwa Chang
- College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 10326, Republic of Korea
| | - Jung-Min Park
- College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 10326, Republic of Korea
| | - Chang Hoon Lee
- College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 10326, Republic of Korea
| | - Bumseok Kim
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Jeollabuk-do 54596, Republic of Korea
| | - Kyung-Chul Choi
- Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungcheongbuk-do 28644, Republic of Korea
| | - Seong-Jin Choi
- Inhalation Toxicology Research Center, Korea Institute of Toxicology, Jeongeup, Jeollabuk-do 56212, Republic of Korea
| | - Kyuhong Lee
- Inhalation Toxicology Research Center, Korea Institute of Toxicology, Jeongeup, Jeollabuk-do 56212, Republic of Korea
| | - Moo-Yeol Lee
- College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 10326, Republic of Korea.
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Henriksen-Lacey M, Carregal-Romero S, Liz-Marzán LM. Current Challenges toward In Vitro Cellular Validation of Inorganic Nanoparticles. Bioconjug Chem 2017; 28:212-221. [PMID: 27709892 PMCID: PMC5247775 DOI: 10.1021/acs.bioconjchem.6b00514] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2016] [Revised: 10/06/2016] [Indexed: 01/09/2023]
Abstract
An impressive development has been achieved toward the production of well-defined "smart" inorganic nanoparticles, in which the physicochemical properties can be controlled and predicted to a high degree of accuracy. Nanoparticle design is indeed highly advanced, multimodal and multitargeting being the norm, yet we do not fully understand the obstacles that nanoparticles face when used in vivo. Increased cooperation between chemists and biochemists, immunologists and physicists, has allowed us to think outside the box, and we are slowly starting to understand the interactions that nanoparticles undergo under more realistic situations. Importantly, such an understanding involves awareness about the limitations when assessing the influence of such inorganic nanoparticles on biological entities and vice versa, as well as the development of new validation strategies.
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Affiliation(s)
- Malou Henriksen-Lacey
- CIC biomaGUNE, Paseo
de Miramón 182, 20014 Donostia − San Sebastián, Spain
- CIBER de Bioingeniería, Biomateriales y Nanomedicina
(CIBER-BBN), 2014 Donostia − San Sebastián, Spain
| | | | - Luis M. Liz-Marzán
- CIC biomaGUNE, Paseo
de Miramón 182, 20014 Donostia − San Sebastián, Spain
- CIBER de Bioingeniería, Biomateriales y Nanomedicina
(CIBER-BBN), 2014 Donostia − San Sebastián, Spain
- Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain
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Friehs E, AlSalka Y, Jonczyk R, Lavrentieva A, Jochums A, Walter JG, Stahl F, Scheper T, Bahnemann D. Toxicity, phototoxicity and biocidal activity of nanoparticles employed in photocatalysis. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY C-PHOTOCHEMISTRY REVIEWS 2016. [DOI: 10.1016/j.jphotochemrev.2016.09.001] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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In vivo proinflammatory activity of generations 0-3 (G0-G3) polyamidoamine (PAMAM) nanoparticles. Inflamm Res 2016; 65:745-55. [PMID: 27338943 DOI: 10.1007/s00011-016-0959-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Revised: 06/02/2016] [Accepted: 06/07/2016] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE AND DESIGN The aim of this study was to determine whether different generations (G) polyamidoamine (PAMAM) dendrimers possess proinflammatory activities in vivo. MATERIAL OR SUBJECTS Several hundred female CD-1 mice were used to test four different PAMAM dendrimers using the murine air pouch model. TREATMENT Mice received appropriate negative and positive controls or G0-G3 PAMAM nanoparticles at 100 and 500 µg/ml into air pouches. METHODS Exudates were harvested after 3, 6, 24 and 48 h. Cell pellets and supernatants were used to determine the number of total leukocytes and neutrophils and to detect the production of several analytes by an antibody array approach, respectively. One-way analysis of variance was used for statistical analysis. RESULTS PAMAM dendrimers rapidly increased a leukocyte influx after 3 h, the vast majority of cells being neutrophils. This was also observed after 6 and 24 h, and resolution of inflammation was noted after 48 h. In general, the increased production of a greater number of analytes detected in the exudates after 6 h correlated with the number of dendrimer generations (G3 > G2 > G1 > G0). CONCLUSIONS PAMAM dendrimers devoid of any delivering molecules possess proinflammatory activities in vivo by themselves, probably via the production of different chemokines released by air pouch lining cells.
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32
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Luis LG, Barreto Â, Trindade T, Soares AMVM, Oliveira M. Effects of emerging contaminants on neurotransmission and biotransformation in marine organisms - An in vitro approach. MARINE POLLUTION BULLETIN 2016; 106:236-244. [PMID: 26988391 DOI: 10.1016/j.marpolbul.2016.02.064] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 02/20/2016] [Accepted: 02/26/2016] [Indexed: 06/05/2023]
Abstract
The effects of gold (ionic form and nanoparticles - AuNPs) and pharmaceuticals (carbamazepine and fluoxetine) on enzymes involved in neurotransmission (acetylcholinesterase - AChE) and biotransformation (glutathione S-transferases - GST) were assessed by their incubation with Mytilus galloprovincialis' hemolymph and subcellular fraction of gills, respectively. AuNPs did not alter enzymatic activities unlike ionic gold that inhibited AChE and GST activities at 2.5 and 0.42mg·L(-1), respectively. Carbamazepine inhibited AChE activity at 500mg·L(-1) and fluoxetine at 1000mg·L(-1). GST was inhibited by carbamazepine at 250mg·L(-1) and by fluoxetine at 125mg·L(-1). Increased AChE activity was found in simultaneous exposures to fluoxetine and bovine serum albumin coated AuNPs (BSA-AuNPs). Concerning GST, in the simultaneous exposures, AuNPs revealed protective effects against carbamazepine (citrate and polyvinylpyrrolidone coated) and fluoxetine (citrate and BSA coated) induced inhibition. However, BSA-AuNPs increased the inhibition caused by carbamazepine. AuNPs demonstrated ability to interfere with other chemicals toxicity justifying further studies.
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Affiliation(s)
- Luis G Luis
- Department of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Ângela Barreto
- Department of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Tito Trindade
- Department of Chemistry & CICECO, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Amadeu M V M Soares
- Department of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Miguel Oliveira
- Department of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal.
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Babin K, Goncalves D, Girard D. Nanoparticles enhance the ability of human neutrophils to exert phagocytosis by a Syk-dependent mechanism. Biochim Biophys Acta Gen Subj 2015; 1850:2276-82. [DOI: 10.1016/j.bbagen.2015.08.006] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2015] [Revised: 07/30/2015] [Accepted: 08/11/2015] [Indexed: 12/21/2022]
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Abstract
Nanoparticles (NPs) present in the environment and in consumer products can cause immunotoxic effects. The immune system is very complex, and in vivo studies are the gold standard for evaluation. Due to the increased amount of NPs that are being developed, cellular screening assays to decrease the amount of NPs that have to be tested in vivo are highly needed. Effects on the unspecific immune system, such as effects on phagocytes, might be suitable for screening for immunotoxicity because these cells mediate unspecific and specific immune responses. They are present at epithelial barriers, in the blood, and in almost all organs. This review summarizes the effects of carbon, metal, and metal oxide NPs used in consumer and medical applications (gold, silver, titanium dioxide, silica dioxide, zinc oxide, and carbon nanotubes) and polystyrene NPs on the immune system. Effects in animal exposures through different routes are compared to the effects on isolated phagocytes. In addition, general problems in the testing of NPs, such as unknown exposure doses, as well as interference with assays are mentioned. NPs appear to induce a specific immunotoxic pattern consisting of the induction of inflammation in normal animals and aggravation of pathologies in disease models. The evaluation of particle action on several phagocyte functions in vitro may provide an indication on the potency of the particles to induce immunotoxicity in vivo. In combination with information on realistic exposure levels, in vitro studies on phagocytes may provide useful information on the health risks of NPs.
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Affiliation(s)
- Eleonore Fröhlich
- Center for Medical Research, Medical University of Graz, Graz, Austria
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35
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Liang L, Cui M, Zhang M, Zheng P, Deng Z, Gao S, Wang X, Zhang X, Wang C, Liu Y, Xie L. Nanoparticles' interference in the evaluation of in vitro toxicity of silver nanoparticles. RSC Adv 2015. [DOI: 10.1039/c5ra05863e] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
We have investigated the interference of silver nanoparticles on the toxicity evaluations. For accurate toxicity evaluation of nanoparticles, it would be very necessary to limit particle concentrations or choose other approaches free from the interference.
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Castiglioni S, Caspani C, Cazzaniga A, Maier JAM. Short- and long-term effects of silver nanoparticles on human microvascular endothelial cells. World J Biol Chem 2014; 5:457-464. [PMID: 25426268 PMCID: PMC4243149 DOI: 10.4331/wjbc.v5.i4.457] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2014] [Revised: 08/01/2014] [Accepted: 09/10/2014] [Indexed: 02/05/2023] Open
Abstract
AIM: To study the response to silver nanoparticles (Ag NP) of human microvascular endothelial cells, protagonists of angiogenesis.
METHODS: We cultured human microvascular endothelial cells and endothelial colony-forming cells in their corresponding growth medium. Stock solutions of Ag NP were prepared in culture medium and sonicated before use. They were added at different concentrations and for different times to culture media. The toxicity of Ag NP was investigated by measuring the reduction of yellow tetrazolium salt to dark purple formazan (MTT assay) at 575 nm. After staining with trypan blue, cell proliferation was assessed by counting viable cells. The lactate dehydrogenase leakage assay was performed on culture media by following the oxidation of NADH to NAD+ and monitoring the reaction kinetically at 340 nm. Reactive oxygen species production was quantified using 2’-7’-dichlorofluorescein diacetate. The alkaline comet assay was performed after mixing the cells with low melting-point agarose. Electrophoresis was then conducted and the samples were stained with ethidium bromide and analyzed with a fluorescence microscope.
RESULTS: Ag NP are cytotoxic in a dose and time dependent fashion for HMEC. At high concentrations, Ag NP determine loss of membrane integrity as demonstrated by the increased activity of lactate dehydrogenase in the culture medium. Ag NP rapidly stimulate the formation of free radicals. However, pre-incubation with Trolox, apocynin, or N-acetyl-L-cysteine, antioxidants which have different structure and act through different mechanisms, is not sufficient to prevent cytotoxicity. Ag NP also induce DNA damage dose-dependently, as shown by comet assay. When exposed to sublethal concentrations of Ag NP for long times, the cells remain viable but are growth retarded. Interestingly, removal of Ag NP partially rescues cell growth. Also genotoxicity is reversible upon removal of Ag NP from culture medium, suggesting that no permanent modifications occur. It is noteworthy that Ag NP are cytotoxic and genotoxic also for endothelial progenitors, in particular for endothelial colony-forming cells, which participate to angiogenesis.
CONCLUSION: Silver nanoparticles are cytotoxic and genotoxic for human microvascular endothelial cells and might become a useful tool to control excessive angiogenesis.
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Kim M, Han CH, Lee MY. Enhancement of platelet aggregation by ursolic Acid and oleanolic Acid. Biomol Ther (Seoul) 2014; 22:254-9. [PMID: 25009707 PMCID: PMC4060080 DOI: 10.4062/biomolther.2014.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2014] [Revised: 03/17/2014] [Accepted: 03/24/2014] [Indexed: 01/05/2023] Open
Abstract
The pentacyclic triterpenoid ursolic acid (UA) and its isomer oleanolic acid (OA) are ubiquitous in food and plant medicine, and thus are easily exposed to the population through natural contact or intentional use. Although they have diverse health benefits, reported cardiovascular protective activity is contentious. In this study, the effect of UA and OA on platelet aggregation was examined on the basis that alteration of platelet activity is a potential process contributing to cardiovascular events. Treatment of UA enhanced platelet aggregation induced by thrombin or ADP, which was concentration-dependent in a range of 5-50 μM. Quite comparable results were obtained with OA, in which OA-treated platelets also exhibited an exaggerated response to either thrombin or ADP. UA treatment potentiated aggregation of whole blood, while OA failed to increase aggregation by thrombin. UA and OA did not affect plasma coagulation assessed by measuring prothrombin time and activated partial thromboplastin time. These results indicate that both UA and OA are capable of making platelets susceptible to aggregatory stimuli, and platelets rather than clotting factors are the primary target of them in proaggregatory activity. These compounds need to be used with caution, especially in the population with a predisposition to cardiovascular events.
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Affiliation(s)
- Mikyung Kim
- College of Pharmacy, Dongguk University, Goyang 410-820
| | - Chang-Ho Han
- Department of Internal Medicine, College of Korean Medicine, Dongguk University, Gyeongju 780-714, Republic of Korea
| | - Moo-Yeol Lee
- College of Pharmacy, Dongguk University, Goyang 410-820
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Kankala S, Kankala RK, Kommidi DR, Mudithanapelli C, Balaboina R, Vadde R, Jonnalagadda SB, Vasam CS. Synthesis and anti-cancer evaluation of steroidal diglycoside–pyrazoline hybrids. RSC Adv 2014. [DOI: 10.1039/c4ra05599c] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
A new series of pyrazoline-steroidal diglycoside hybrids were synthesized via catalyzed cyclocondensation of the corresponding chalcones, screened for in vitro cytotoxic activity and the SAR deduced.
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Affiliation(s)
- Shravankumar Kankala
- Department of Chemistry
- Kakatiya University
- Warangal, India
- School of Chemistry & Physics
- University of Kwazulu-Natal
| | - Ranjith Kumar Kankala
- Institute of Biotechnology
- National Dong-Hwa University
- Hualien 974, Republic of China
| | | | | | | | - Ravinder Vadde
- Department of Chemistry
- Kakatiya University
- Warangal, India
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