Organic Nanoparticle Genotoxicity: Current Understanding and Future Testing Needs
Keywords:
Chitosan, DNA damage, Genotoxicity, Liposomes, Organic nanoparticles
Abstract
Organic nanoparticles derived from biocompatible materials like chitosan, alginate, and lipids have garnered immense interest for drug delivery, bioimaging, and other biomedical applications. However, as their use rapidly expands, a comprehensive evaluation of their potential genotoxicity is crucial to ensure safe implementation. This review provides an in-depth analysis of the genotoxic risks associated with these organic nanoparticles. The review elucidates how the unique physicochemical properties of organic nanoparticles can induce genetic damage through mechanisms such as direct DNA binding, oxidative stress, inflammation, and impairment of DNA repair pathways. Importantly, this genotoxicity can occur even in the absence of overt cytotoxicity, leading to heritable mutations and long-term adverse effects like cancer and reproductive abnormalities. A critical assessment of established and emerging genotoxicity testing methods, including their strengths, limitations, and opportunities for standardization, is presented. The review synthesizes findings from existing in vitro and in vivo studies, revealing the contrasting genotoxic profiles of different organic nanoparticle formulations and exposure scenarios. Furthermore, the review provides insights into the multifaceted factors influencing nanoparticle genotoxicity, guiding the strategic engineering of safer designs. This comprehensive analysis underscores the pivotal importance of rigorous genotoxicity screening in the responsible development of organic nanomaterials. By harmonizing their innovative capabilities with a commitment to genetic integrity, this review paves the way for realizing the vast potential of organic nanoparticles while safeguarding human and environmental health.
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Author Biography
Muhammad Ikhlas Arsul, Universitas Islam Negeri Alauddin
References
Abbasi, R., Shineh, G., Mobaraki, M., Doughty, S., & Tayebi, L. (2023). Structural parameters of nanoparticles affecting their toxicity for biomedical applications: a review. Journal of Nanoparticle Research, 25(3), 43. https://doi.org/10.1007/s11051-023-05690-w
Abou-Saleh, H., Younes, N., Rasool, K., Younis, M. H., Prieto, R. M., Yassine, H. M., Mahmoud, K. A., Pintus, G., & Nasrallah, G. K. (2019). Impaired liver size and compromised neurobehavioral activity are elicited by chitosan nanoparticles in the zebrafish embryo model. Nanomaterials, 9(1). https://doi.org/10.3390/nano9010122
Afantitis, A., Melagraki, G., Isigonis, P., Tsoumanis, A., Varsou, D. D., Valsami-Jones, E., Papadiamantis, A., Ellis, L.-J. A., Sarimveis, H., Doganis, P., Karatzas, P., Tsiros, P., Liampa, I., Lobaskin, V., Greco, D., Serra, A., Kinaret, P. A. S., Saarimäki, L. A., Grafström, R., … Lynch, I. (2020). NanoSolveIT Project: Driving nanoinformatics research to develop innovative and integrated tools for in silico nanosafety assessment. Computational and Structural Biotechnology Journal, 18, 583–602. https://doi.org/https://doi.org/10.1016/j.csbj.2020.02.023
Akbarzadeh, A., Rezaei-Sadabady, R., Davaran, S., Joo, S. W., Zarghami, N., Hanifehpour, Y., Samiei, M., Kouhi, M., & Nejati-Koshki, K. (2013). Liposome: classification, preparation, and applications. Nanoscale Research Letters, 8(1), 102. https://doi.org/10.1186/1556-276X-8-102
Amin, M. K., & Boateng, J. S. (2022). Enhancing Stability and Mucoadhesive Properties of Chitosan Nanoparticles by Surface Modification with Sodium Alginate and Polyethylene Glycol for Potential Oral Mucosa Vaccine Delivery. Marine Drugs, 20(3). https://doi.org/10.3390/md20030156
Araldi, R. P., de Melo, T. C., Mendes, T. B., de Sá Júnior, P. L., Nozima, B. H. N., Ito, E. T., de Carvalho, R. F., de Souza, E. B., & de Cassia Stocco, R. (2015). Using the comet and micronucleus assays for genotoxicity studies: A review. Biomedicine & Pharmacotherapy, 72, 74–82. https://doi.org/https://doi.org/10.1016/j.biopha.2015.04.004
Bhattacharya, S., Zhang, Q., Carmichael, P. L., Boekelheide, K., & Andersen, M. E. (2011). Toxicity Testing in the 21st Century: Defining New Risk Assessment Approaches Based on Perturbation of Intracellular Toxicity Pathways. PLOS ONE, 6(6), e20887-. https://doi.org/10.1371/journal.pone.0020887
Blanco, E., Shen, H., & Ferrari, M. (2015). Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology, 33(9), 941–951. https://doi.org/10.1038/nbt.3330
Bozzuto, G., & Molinari, A. (2015). Liposomes as nanomedical devices. In International Journal of Nanomedicine (Vol. 10, pp. 975–999). Dove Medical Press Ltd. https://doi.org/10.2147/IJN.S68861
Bryce, S. M., Shi, J., Nicolette, J., Diehl, M., Sonders, P., Avlasevich, S., Raja, S., Bemis, J. C., & Dertinger, S. D. (2010). High content flow cytometric micronucleus scoring method is applicable to attachment cell lines. Environmental and Molecular Mutagenesis, 51(3), 260–266. https://doi.org/https://doi.org/10.1002/em.20544
Buoso, E., Biundo, F., & Attanzio, A. (2022). New Therapeutic Approaches against Inflammation and Oxidative Stress in Neurodegeneration. Oxidative Medicine and Cellular Longevity, 2022(1), 9824350. https://doi.org/https://doi.org/10.1155/2022/9824350
Cahn, D., & Duncan, G. A. (2022). High-Density Branched PEGylation for Nanoparticle Drug Delivery. Cellular and Molecular Bioengineering, 15(5), 355–366. https://doi.org/10.1007/s12195-022-00727-x
Carriere, M., Sauvaigo, S., Douki, T., & Ravanat, J.-L. (2017). Impact of nanoparticles on DNA repair processes: current knowledge and working hypotheses. Mutagenesis, 32(1), 203–213. https://doi.org/10.1093/mutage/gew052
Chou, C.-M., Mi, F.-L., Horng, J.-L., Lin, L.-Y., Tsai, M.-L., Liu, C.-L., Lu, K.-Y., Chu, C.-Y., Chen, Y.-T., Lee, Y.-L. A., & Cheng, C.-H. (2020). Characterization and toxicology evaluation of low molecular weight chitosan on zebrafish. Carbohydrate Polymers, 240, 116164. https://doi.org/https://doi.org/10.1016/j.carbpol.2020.116164
Cinat, D., Coppes, R. P., & Barazzuol, L. (2021). DNA Damage-Induced Inflammatory Microenvironment and Adult Stem Cell Response. In Frontiers in Cell and Developmental Biology (Vol. 9). Frontiers Media S.A. https://doi.org/10.3389/fcell.2021.729136
Collins, A. R. (2004). The comet assay for DNA damage and repair. Molecular Biotechnology, 26(3), 249–261. https://doi.org/10.1385/MB:26:3:249
Cordelli, E., Bignami, M., & Pacchierotti, F. (2021). Comet assay: a versatile but complex tool in genotoxicity testing. Toxicology Research, 10(1), 68–78. https://doi.org/10.1093/toxres/tfaa093
Din, F. U., Aman, W., Ullah, I., Qureshi, O. S., Mustapha, O., Shafique, S., & Zeb, A. (2017). Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. In International Journal of Nanomedicine (Vol. 12, pp. 7291–7309). Dove Medical Press Ltd. https://doi.org/10.2147/IJN.S146315
Divya, L., Raju, M. B., & Raut, S. Y. (2014). Chitosan-Based Micro and Nanoparticles: A Promising System for Drug Delivery. Research J. Pharm. and Tech, 7(12). www.rjptonline.org
Doak, S. H., & Dusinska, M. (2017). NanoGenotoxicology: present and the future. Mutagenesis, 32(1), 1–4. https://doi.org/10.1093/mutage/gew066
Dusinska, M., Rundén-Pran, E., El Yamani, N., Fjellsbø, L. M., & Collins, A. (2016). Application of the Comet Assay in Nanotoxicology. In D. Anderson & A. Dhawan (Eds.), The Comet Assay in Toxicology (p. 0). The Royal Society of Chemistry. https://doi.org/10.1039/9781782622895-00477
Eastmond, D. A., Hartwig, A., Anderson, D., Anwar, W. A., Cimino, M. C., Dobrev, I., Douglas, G. R., Nohmi, T., Phillips, D. H., & Vickers, C. (2009). Mutagenicity testing for chemical risk assessment: update of the WHO/IPCS Harmonized Scheme. Mutagenesis, 24(4), 341–349. https://doi.org/10.1093/mutage/gep014
Elespuru, R., Pfuhler, S., Aardema, M. J., Chen, T., Doak, S. H., Doherty, A., Farabaugh, C. S., Kenny, J., Manjanatha, M., Mahadevan, B., Moore, M. M., Ouédraogo, G., Stankowski Jr, L. F., & Tanir, J. Y. (2018). Genotoxicity Assessment of Nanomaterials: Recommendations on Best Practices, Assays, and Methods. Toxicological Sciences, 164(2), 391–416. https://doi.org/10.1093/toxsci/kfy100
Elnaggar, Y. S. R., Etman, S. M., Abdelmonsif, D. A., & Abdallah, O. Y. (2015). Intranasal Piperine-Loaded Chitosan Nanoparticles as Brain-Targeted Therapy in Alzheimer’s Disease: Optimization, Biological Efficacy, and Potential Toxicity. Journal of Pharmaceutical Sciences, 104(10), 3544–3556. https://doi.org/10.1002/jps.24557
Elsabahy, M., & Wooley, K. L. (2012). Design of polymeric nanoparticles for biomedical delivery applications. Chem. Soc. Rev., 41(7), 2545–2561. https://doi.org/10.1039/C2CS15327K
Evans, M. D., Dizdaroglu, M., & Cooke, M. S. (2004). Oxidative DNA damage and disease: induction, repair and significance. Mutation Research/Reviews in Mutation Research, 567(1), 1–61. https://doi.org/https://doi.org/10.1016/j.mrrev.2003.11.001
Gajewicz, A., Rasulev, B., Dinadayalane, T. C., Urbaszek, P., Puzyn, T., Leszczynska, D., & Leszczynski, J. (2012). Advancing risk assessment of engineered nanomaterials: Application of computational approaches. Advanced Drug Delivery Reviews, 64(15), 1663–1693. https://doi.org/https://doi.org/10.1016/j.addr.2012.05.014
Gonzalez, L., Sanderson, B. J. S., & Kirsch-Volders, M. (2011). Adaptations of the in vitro MN assay for the genotoxicity assessment of nanomaterials. Mutagenesis, 26(1), 185–191. https://doi.org/10.1093/mutage/geq088
Gupta, A., Eral, H. B., Hatton, T. A., & Doyle, P. S. (2016). Nanoemulsions: Formation, properties and applications. In Soft Matter (Vol. 12, Issue 11, pp. 2826–2841). Royal Society of Chemistry. https://doi.org/10.1039/c5sm02958a
Habas, K., Abdulmwli, M., Demir, E., Jacob, B. K., Najafzadeh, M., & Anderson, D. (2018). DNA damage protection by bulk and nano forms of quercetin in lymphocytes of patients with chronic obstructive pulmonary disease exposed to the food mutagen 2-amino-3-methylimidazo [4,5-f]quinolone (IQ). Environmental Research, 166, 10–15. https://doi.org/https://doi.org/10.1016/j.envres.2018.05.012
Halder, A. K., Melo, A., & Cordeiro, M. N. D. S. (2020). A unified in silico model based on perturbation theory for assessing the genotoxicity of metal oxide nanoparticles. Chemosphere, 244, 125489. https://doi.org/https://doi.org/10.1016/j.chemosphere.2019.125489
Hamouda, R. A., Salman, A. S., Alharbi, A. A., Alhasani, R. H., & Elshamy, M. M. (2021). Assessment of the antigenotoxic effects of alginate and ZnO/alginate–nanocomposites extracted from brown alga fucus vesiculosus in mice. Polymers, 13(21). https://doi.org/10.3390/polym13213839
Honary, S., & Zahir, F. (2013). Effect of zeta potential on the properties of nano-drug delivery systems - A review (Part 2). Tropical Journal of Pharmaceutical Research, 12(2), 265–273. https://doi.org/10.4314/tjpr.v12i2.20
Hu, Y. L., Qi, W., Han, F., Shao, J. Z., & Gao, J. Q. (2011). Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model. International Journal of Nanomedicine, 6, 3351–3359. https://doi.org/10.2147/ijn.s25853
Huo, S., Jin, S., Ma, X., Xue, X., Yang, K., Kumar, A., Wang, P. C., Zhang, J., Hu, Z., & Liang, X.-J. (2014). Ultrasmall Gold Nanoparticles as Carriers for Nucleus-Based Gene Therapy Due to Size-Dependent Nuclear Entry. ACS Nano, 8(6), 5852–5862. https://doi.org/10.1021/nn5008572
Inglut, C. T., Sorrin, A. J., Kuruppu, T., Vig, S., Cicalo, J., Ahmad, H., & Huang, H. C. (2020). Immunological and toxicological considerations for the design of liposomes. In Nanomaterials (Vol. 10, Issue 2). MDPI AG. https://doi.org/10.3390/nano10020190
Iwaoka, S., Nakamura, T., Takano, S., Tsuchiya, S., & Aramaki, Y. (2006). Cationic liposomes induce apoptosis through p38 MAP kinase–caspase-8–Bid pathway in macrophage-like RAW264.7 cells. Journal of Leukocyte Biology, 79(1), 184–191. https://doi.org/10.1189/jlb.0405181
Jokerst, J. V, Lobovkina, T., Zare, R. N., & Gambhir, S. S. (2011). Nanoparticle PEGylation for Imaging and Therapy. Nanomedicine, 6(4), 715–728. https://doi.org/10.2217/nnm.11.19
Kazimirova, A., Baranokova, M., Staruchova, M., Drlickova, M., Volkovova, K., & Dusinska, M. (2019). Titanium dioxide nanoparticles tested for genotoxicity with the comet and micronucleus assays in vitro, ex vivo and in vivo. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 843, 57–65. https://doi.org/https://doi.org/10.1016/j.mrgentox.2019.05.001
Kermanizadeh, A., Gaiser, B. K., Ward, M. B., & Stone, V. (2013). Primary human hepatocytes versus hepatic cell line: assessing their suitability for in vitro nanotoxicology. Nanotoxicology, 7(7), 1255–1271. https://doi.org/10.3109/17435390.2012.734341
Kim, J., Cho, H., Lim, D. K., Joo, M. K., & Kim, K. (2023). Perspectives for Improving the Tumor Targeting of Nanomedicine via the EPR Effect in Clinical Tumors. In International Journal of Molecular Sciences (Vol. 24, Issue 12). MDPI. https://doi.org/10.3390/ijms241210082
Kim, S., Kim, M., Jung, S., Kwon, K., Park, J., Kim, S., Kwon, I., & Tae, G. (2019). Co-delivery of therapeutic protein and catalase-mimic nanoparticle using a biocompatible nanocarrier for enhanced therapeutic effect. Journal of Controlled Release, 309, 181–189. https://doi.org/https://doi.org/10.1016/j.jconrel.2019.07.038
Kirsch-Volders, M., Sofuni, T., Aardema, M., Albertini, S., Eastmond, D., Fenech, M., Ishidate, M., Kirchner, S., Lorge, E., Morita, T., Norppa, H., Surrallés, J., Vanhauwaert, A., & Wakata, A. (2003). Report from the in vitro micronucleus assay working group. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 540(2), 153–163. https://doi.org/https://doi.org/10.1016/j.mrgentox.2003.07.005
Knudsen, K. B., Northeved, H., Kumar EK, P., Permin, A., Gjetting, T., Andresen, T. L., Larsen, S., Wegener, K. M., Lykkesfeldt, J., Jantzen, K., Loft, S., Møller, P., & Roursgaard, M. (2015). In vivo toxicity of cationic micelles and liposomes. Nanomedicine: Nanotechnology, Biology and Medicine, 11(2), 467–477. https://doi.org/https://doi.org/10.1016/j.nano.2014.08.004
Kohl, Y., Rundén-Pran, E., Mariussen, E., Hesler, M., Yamani, N. El, Longhin, E. M., & Dusinska, M. (2020). Genotoxicity of nanomaterials: Advanced in vitro models and high throughput methods for human hazard assessment—a review. In Nanomaterials (Vol. 10, Issue 10, pp. 1–25). MDPI AG. https://doi.org/10.3390/nano10101911
Kumar, P. R., & Vijaya, L. A. (2020). An overview on nanobased drug delivery system. Research Journal of Pharmacy and Technology, 13(10), 4996. https://doi.org/10.5958/0974-360x.2020.00875.6
Kumar, V., Sharma, N., & Maitra, S. S. (2017). In vitro and in vivo toxicity assessment of nanoparticles. International Nano Letters, 7(4), 243–256. https://doi.org/10.1007/s40089-017-0221-3
Kuo, B., Beal, M. A., Wills, J. W., White, P. A., Marchetti, F., Nong, A., Barton-Maclaren, T. S., Houck, K., & Yauk, C. L. (2022). Comprehensive interpretation of in vitro micronucleus test results for 292 chemicals: from hazard identification to risk assessment application. Archives of Toxicology, 96(7), 2067–2085. https://doi.org/10.1007/s00204-022-03286-2
Lewinski, N., Colvin, V., & Drezek, R. (2008). Cytotoxicity of Nanoparticles. Small, 4(1), 26–49. https://doi.org/https://doi.org/10.1002/smll.200700595
Liang, H., Peng, B., Dong, C., Liu, L., Mao, J., Wei, S., Wang, X., Xu, H., Shen, J., Mao, H.-Q., Gao, X., Leong, K. W., & Chen, Y. (2018). Cationic nanoparticle as an inhibitor of cell-free DNA-induced inflammation. Nature Communications, 9(1), 4291. https://doi.org/10.1038/s41467-018-06603-5
Liu, J., Liu, Z., Pang, Y., & Zhou, H. (2022). The interaction between nanoparticles and immune system: application in the treatment of inflammatory diseases. Journal of Nanobiotechnology, 20(1), 127. https://doi.org/10.1186/s12951-022-01343-7
Liu, Q., Sun, M., Wang, T., Zhou, Y., Sun, M., Li, H., Liu, Y., & Xu, A. (2023). The Differential Antagonistic Ability of Curcumin against Cytotoxicity and Genotoxicity Induced by Distinct Heavy Metals. Toxics, 11(3). https://doi.org/10.3390/toxics11030233
Loh, J. W., Yeoh, G., Saunders, M., & Lim, L.-Y. (2010). Uptake and cytotoxicity of chitosan nanoparticles in human liver cells. Toxicology and Applied Pharmacology, 249(2), 148–157. https://doi.org/https://doi.org/10.1016/j.taap.2010.08.029
Lohani, A., Verma, A., Joshi, H., Yadav, N., & Karki, N. (2014). Nanotechnology-Based Cosmeceuticals. International Scholarly Research Notices, 2014(1), 843687. https://doi.org/https://doi.org/10.1155/2014/843687
Lu, H., Zhang, S., Wang, J., & Chen, Q. (2021). A Review on Polymer and Lipid-Based Nanocarriers and Its Application to Nano-Pharmaceutical and Food-Based Systems. In Frontiers in Nutrition (Vol. 8). Frontiers Media S.A. https://doi.org/10.3389/fnut.2021.783831
Lu, X., & Zhang, K. (2018). PEGylation of therapeutic oligonucletides: From linear to highly branched PEG architectures. Nano Research, 11(10), 5519–5534. https://doi.org/10.1007/s12274-018-2131-8
Lu, Y., Liu, Y., & Yang, C. (2017). Evaluating In Vitro DNA Damage Using Comet Assay. JoVE, 128, e56450. https://doi.org/doi:10.3791/56450
Luan, Y., & Honma, M. (2022). Genotoxicity testing and recent advances. Genome Instability & Disease, 3(1), 1–21. https://doi.org/10.1007/s42764-021-00058-7
Ma, T., Arroyo, N., Janot, J. M., Picaud, F., & Balme, S. (2021). Conformation of polyethylene glycol inside confined space: simulation and experimental approaches. Nanomaterials, 11(1), 1–18. https://doi.org/10.3390/nano11010244
Magdolenova, Z., Bilaničová, D., Pojana, G., Fjellsbø, L. M., Hudecova, A., Hasplova, K., Marcomini, A., & Dusinska, M. (2012). Impact of agglomeration and different dispersions of titanium dioxide nanoparticles on the human related in vitro cytotoxicity and genotoxicity. J. Environ. Monit., 14(2), 455–464. https://doi.org/10.1039/C2EM10746E
Magdolenova, Z., Drlickova, M., Henjum, K., Rundén-Pran, E., Tulinska, J., Bilanicova, D., Pojana, G., Kazimirova, A., Barancokova, M., Kuricova, M., Liskova, A., Staruchova, M., Ciampor, F., Vavra, I., Lorenzo, Y., Collins, A., Rinna, A., Fjellsbø, L., Volkovova, K., … Dusinska, M. (2015). Coating-dependent induction of cytotoxicity and genotoxicity of iron oxide nanoparticles. Nanotoxicology, 9(sup1), 44–56. https://doi.org/10.3109/17435390.2013.847505
Maurya, D. K. (2014). HaloJ: An imageJ program for semiautomatic quantification of DNA damage at single-cell level. International Journal of Toxicology, 33(5), 362–366. https://doi.org/10.1177/1091581814549961
Mirakabadi, A. Z., & Moradhaseli, S. (2013). Comparative Cytotoxic Evaluation of Free and Sodium Alginate Nanoparticle-Encapsulated ICD-85 on Primary Lamb Kidney Cells. Iran J Cancer Prev, 6(3), 151–159.
Møller, P., Azqueta, A., Boutet-Robinet, E., Koppen, G., Bonassi, S., Milić, M., Gajski, G., Costa, S., Teixeira, J. P., Costa Pereira, C., Dusinska, M., Godschalk, R., Brunborg, G., Gutzkow, K. B., Giovannelli, L., Cooke, M. S., Richling, E., Laffon, B., Valdiglesias, V., … Langie, S. A. S. (2020). Minimum Information for Reporting on the Comet Assay (MIRCA): recommendations for describing comet assay procedures and results. Nature Protocols, 15(12), 3817–3826. https://doi.org/10.1038/s41596-020-0398-1
Nazarparvar-Noshadi, M., Ezzati Nazhad Dolatabadi, J., Rasoulzadeh, Y., Mohammadian, Y., & Shanehbandi, D. (2020). Apoptosis and DNA damage induced by silica nanoparticles and formaldehyde in human lung epithelial cells. Environmental Science and Pollution Research, 27(15), 18592–18601. https://doi.org/10.1007/s11356-020-08191-8
Omar Zaki, S. S., Katas, H., & Hamid, Z. A. (2015). Lineage-related and particle size-dependent cytotoxicity of chitosan nanoparticles on mouse bone marrow-derived hematopoietic stem and progenitor cells. Food and Chemical Toxicology, 85, 31–44. https://doi.org/https://doi.org/10.1016/j.fct.2015.05.017
Osman IF, Jacob BK, & Anderson D. (2011). Effect of nanoparticles on human cells from healthy individuals and patients with respiratory diseases. J Biomed Nanotechnol, 7(1), 26–27.
Owens, D. E., & Peppas, N. A. (2006). Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. International Journal of Pharmaceutics, 307(1), 93–102. https://doi.org/https://doi.org/10.1016/j.ijpharm.2005.10.010
Paolicelli, P., de la Fuente, M., Sánchez, A., Seijo, B., & Alonso, M. J. (2009). Chitosan nanoparticles for drug delivery to the eye. Expert Opinion on Drug Delivery, 6(3), 239–253. https://doi.org/10.1517/17425240902762818
Parmar, K., Patel, J., & Pathak, Y. (2022). Factors Affecting the Clearance and Biodistribution of Polymeric Nanoparticles. In J. K. Patel & Y. V Pathak (Eds.), Pharmacokinetics and Pharmacodynamics of Nanoparticulate Drug Delivery Systems (pp. 261–272). Springer International Publishing. https://doi.org/10.1007/978-3-030-83395-4_14
Patra, J. K., Das, G., Fraceto, L. F., Campos, E. V. R., Rodriguez-Torres, M. del P., Acosta-Torres, L. S., Diaz-Torres, L. A., Grillo, R., Swamy, M. K., Sharma, S., Habtemariam, S., & Shin, H.-S. (2018). Nano based drug delivery systems: recent developments and future prospects. Journal of Nanobiotechnology, 16(1), 71. https://doi.org/10.1186/s12951-018-0392-8
Pawar, S. N., & Edgar, K. J. (2012). Alginate derivatization: A review of chemistry, properties and applications. Biomaterials, 33(11), 3279–3305. https://doi.org/https://doi.org/10.1016/j.biomaterials.2012.01.007
Prabha, S., Arya, G., Chandra, R., Ahmed, B., & Nimesh, S. (2016). Effect of size on biological properties of nanoparticles employed in gene delivery. In Artificial Cells, Nanomedicine and Biotechnology (Vol. 44, Issue 1, pp. 83–91). Taylor and Francis Ltd. https://doi.org/10.3109/21691401.2014.913054
Preaubert, L., Courbiere, B., Achard, V., Tassistro, V., Greco, F., Orsiere, T., Bottero, J.-Y., Rose, J., Auffan, M., & Perrin, J. (2016). Cerium dioxide nanoparticles affect in vitro fertilization in mice. Nanotoxicology, 10(1), 111–117. https://doi.org/10.3109/17435390.2015.1030792
Rao, J. P., & Geckeler, K. E. (2011). Polymer nanoparticles: Preparation techniques and size-control parameters. Progress in Polymer Science, 36(7), 887–913. https://doi.org/https://doi.org/10.1016/j.progpolymsci.2011.01.001
Rivera Gil, P., Oberdörster, G., Elder, A., Puntes, V., & Parak, W. J. (2010). Correlating Physico-Chemical with Toxicological Properties of Nanoparticles: The Present and the Future. ACS Nano, 4(10), 5527–5531. https://doi.org/10.1021/nn1025687
Sadaqa, E., Utami, R. A., & Mudhakir, D. (2024). In vitro cytotoxic and genotoxic effects of Phyllanthus niruri extract loaded chitosan nanoparticles in TM4 cells and their influence on spermatogenesis. Pharmacia, 71, 1–14. https://doi.org/https://doi.org/10.3897/pharmacia.71.e112138
Sanità, G., Carrese, B., & Lamberti, A. (2020). Nanoparticle Surface Functionalization: How to Improve Biocompatibility and Cellular Internalization. In Frontiers in Molecular Biosciences (Vol. 7). Frontiers Media S.A. https://doi.org/10.3389/fmolb.2020.587012
Saravanan, V., & Tippavajhala, V. K. (2022). Quantum Dots: Targeted and Traceable Drug Delivery System. Research Journal of Pharmacy and Technology, 15(12), 5895–5902. https://doi.org/10.52711/0974-360X.2022.00994
Sercombe, L., Veerati, T., Moheimani, F., Wu, S. Y., Sood, A. K., & Hua, S. (2015). Advances and challenges of liposome assisted drug delivery. In Frontiers in Pharmacology (Vol. 6, Issue DEC). Frontiers Media S.A. https://doi.org/10.3389/fphar.2015.00286
Sestili, P. (2009). The Fast-Halo Assay for the Assessment of DNA Damage at the Single-Cell Level. In S. Vengrova & J. Z. Dalgaard (Eds.), DNA Replication: Methods and Protocols (pp. 517–533). Humana Press. https://doi.org/10.1007/978-1-60327-815-7_30
Sestili, P., Calcabrini, C., Diaz, A. R., Fimognari, C., & Stocchi, V. (2017). The Fast-Halo Assay for the Detection of DNA Damage. In V. V Didenko (Ed.), Fast Detection of DNA Damage: Methods and Protocols (pp. 75–93). Springer New York. https://doi.org/10.1007/978-1-4939-7187-9_6
Sestili, P., Martinelli, C., & Stocchi, V. (2006). The fast halo assay: An improved method to quantify genomic DNA strand breakage at the single-cell level. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 607(2), 205–214. https://doi.org/https://doi.org/10.1016/j.mrgentox.2006.04.018
Shah, V., Taratula, O., Garbuzenko, O. B., Patil, M. L., Savla, R., Zhang, M., & Minko, T. (2013). Genotoxicity of Different Nanocarriers: Possible Modifications for the Delivery of Nucleic Acids. Curr Drug Discov Technol, 10(1), 8–15.
Sharma, V., Anderson, D., & Dhawan, A. (2012). Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2). Apoptosis, 17(8), 852–870. https://doi.org/10.1007/s10495-012-0705-6
Shi, L., Zhang, J., Zhao, M., Tang, S., Cheng, X., Zhang, W., Li, W., Liu, X., Peng, H., & Wang, Q. (2021). Effects of polyethylene glycol on the surface of nanoparticles for targeted drug delivery. Nanoscale, 13(24), 10748–10764. https://doi.org/10.1039/D1NR02065J
Shukla, R. K., Badiye, A., Vajpayee, K., & Kapoor, N. (2021). Genotoxic Potential of Nanoparticles: Structural and Functional Modifications in DNA. In Frontiers in Genetics (Vol. 12). Frontiers Media S.A. https://doi.org/10.3389/fgene.2021.728250
Singh, M. (2021). Assessing Nucleic Acid: CationicCationic Nanoparticle Interaction for Gene DeliveryGene delivery. In K. Narayanan (Ed.), Bio-Carrier Vectors: Methods and Protocols (pp. 43–55). Springer US. https://doi.org/10.1007/978-1-0716-0943-9_4
Singh, N., Manshian, B., Jenkins, G. J. S., Griffiths, S. M., Williams, P. M., Maffeis, T. G. G., Wright, C. J., & Doak, S. H. (2009). NanoGenotoxicology: The DNA damaging potential of engineered nanomaterials. Biomaterials, 30(23), 3891–3914. https://doi.org/https://doi.org/10.1016/j.biomaterials.2009.04.009
Singhal, A., Morris, V. B., Labhasetwar, V., & Ghorpade, A. (2013). Nanoparticle-mediated catalase delivery protects human neurons from oxidative stress. Cell Death and Disease, 4(11). https://doi.org/10.1038/cddis.2013.362
Sommer, S., Buraczewska, I., & Kruszewski, M. (2020). Micronucleus assay: The state of art, and future directions. In International Journal of Molecular Sciences (Vol. 21, Issue 4). MDPI AG. https://doi.org/10.3390/ijms21041534
Spadari, C. de C., de Bastiani, F. W. M. da S., Lopes, L. B., & Ishida, K. (2019). Alginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis. International Journal of Nanomedicine, 14, 5187–5199. https://doi.org/10.2147/IJN.S205350
Suk, J. S., Xu, Q., Kim, N., Hanes, J., & Ensign, L. M. (2016). PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Advanced Drug Delivery Reviews, 99, 28–51. https://doi.org/https://doi.org/10.1016/j.addr.2015.09.012
Thai, H., Thuy Nguyen, C., Thi Thach, L., Thi Tran, M., Duc Mai, H., Thi Thu Nguyen, T., Duc Le, G., Van Can, M., Dai Tran, L., Long Bach, G., Ramadass, K., Sathish, C. I., & Van Le, Q. (2020). Characterization of chitosan/alginate/lovastatin nanoparticles and investigation of their toxic effects in vitro and in vivo. Scientific Reports, 10(1), 909. https://doi.org/10.1038/s41598-020-57666-8
Thomas, D., & Latha, M. S. (2023). Alginate Based Nanocarriers for Controlled Drug Delivery Applications. In S. Jana & S. Jana (Eds.), Alginate Biomaterial: Drug Delivery Strategies and Biomedical Engineering (pp. 61–83). Springer Nature Singapore. https://doi.org/10.1007/978-981-19-6937-9_3
Tirichen, H., Yaigoub, H., Xu, W., Wu, C., Li, R., & Li, Y. (2021). Mitochondrial Reactive Oxygen Species and Their Contribution in Chronic Kidney Disease Progression Through Oxidative Stress. In Frontiers in Physiology (Vol. 12). Frontiers Media S.A. https://doi.org/10.3389/fphys.2021.627837
Tønnesen, H. H., & Karlsen, J. (2002). Alginate in Drug Delivery Systems. Drug Development and Industrial Pharmacy, 28(6), 621–630. https://doi.org/10.1081/DDC-120003853
Van Haute, D., Liu, A. T., & Berlin, J. M. (2018). Coating Metal Nanoparticle Surfaces with Small Organic Molecules Can Reduce Nonspecific Cell Uptake. ACS Nano, 12(1), 117–127. https://doi.org/10.1021/acsnano.7b03025
Vidya, G., Gladwin, V., & Chand, P. (2015). A comprehensive review on clinical applications of comet assay. In Journal of Clinical and Diagnostic Research (Vol. 9, Issue 3, pp. GE01–GE05). Journal of Clinical and Diagnostic Research. https://doi.org/10.7860/JCDR/2015/12062.5622
Wang, Y., Zhou, J., Liu, L., Huang, C., Zhou, D., & Fu, L. (2016). Characterization and toxicology evaluation of chitosan nanoparticles on the embryonic development of zebrafish, Danio rerio. Carbohydrate Polymers, 141, 204–210. https://doi.org/https://doi.org/10.1016/j.carbpol.2016.01.012
Ways, T. M. M., Lau, W. M., & Khutoryanskiy, V. V. (2018). Chitosan and its derivatives for application in mucoadhesive drug delivery systems. In Polymers (Vol. 10, Issue 3). MDPI AG. https://doi.org/10.3390/polym10030267
Xie, D., Hu, J., Yang, Z., Wu, T., Xu, W., Meng, Q., Cao, K., & Luo, X. (2022). Vitamin Supplementation Protects against Nanomaterial-Induced Oxidative Stress and Inflammation Damages: A Meta-Analysis of In Vitro and In Vivo Studies. Nutrients, 14. https://api.semanticscholar.org/CorpusID:249217931
Ye, L., Kollie, L., Liu, X., Guo, W., Ying, X., Zhu, J., Yang, S., & Yu, M. (2021). Antitumor activity and potential mechanism of novel fullerene derivative nanoparticles. In Molecules (Vol. 26, Issue 11). MDPI AG. https://doi.org/10.3390/molecules26113252
Ye, Z., Shi, Y., Lees-Miller, S. P., & Tainer, J. A. (2021). Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy. In Frontiers in Immunology (Vol. 12). Frontiers Media S.A. https://doi.org/10.3389/fimmu.2021.797880
Yu, Z., Li, Q., Wang, J., Yu, Y., Wang, Y., Zhou, Q., & Li, P. (2020). Reactive Oxygen Species-Related Nanoparticle Toxicity in the Biomedical Field. Nanoscale Research Letters, 15(1), 115. https://doi.org/10.1186/s11671-020-03344-7
Yuan, Z., Li, Y., Hu, Y., You, J., Higashisaka, K., Nagano, K., Tsutsumi, Y., & Gao, J. (2016). Chitosan nanoparticles and their Tween 80 modified counterparts disrupt the developmental profile of zebrafish embryos. International Journal of Pharmaceutics, 515(1), 644–656. https://doi.org/https://doi.org/10.1016/j.ijpharm.2016.10.071
Zhanataev, A. K., Anisina, E. A., Kulakova, A. V, Shilovskiy, I. P., Lisitsyn, A. A., Koloskova, O. O., Khaitov, M. R., & Durnev, A. D. (2020). Genotoxicity of cationic lipopeptide nanoparticles. Toxicology Letters, 328, 1–6. https://doi.org/https://doi.org/10.1016/j.toxlet.2020.04.011
Zielińska, A., Costa, B., Ferreira, M. V., Miguéis, D., Louros, J. M. S., Durazzo, A., Lucarini, M., Eder, P., Chaud, M. V., Morsink, M., Willemen, N., Severino, P., Santini, A., & Souto, E. B. (2020). Nanotoxicology and nanosafety: Safety-by-design and testing at a glance. In International Journal of Environmental Research and Public Health (Vol. 17, Issue 13, pp. 1–22). MDPI AG. https://doi.org/10.3390/ijerph17134657
Zohri, M., Arefian, E., Akbari Javar, H., Gazori, T., Aghaee-Bakhtiari, S. H., Taheri, M., Fatahi, Y., Azadi, A., Khoshayand, M. R., & Ghahremani, M. H. (2021). Potential of chitosan/alginate nanoparticles as a non-viral vector for gene delivery: Formulation and optimization using D-optimal design. Materials Science and Engineering: C, 128, 112262. https://doi.org/https://doi.org/10.1016/j.msec.2021.112262
Abou-Saleh, H., Younes, N., Rasool, K., Younis, M. H., Prieto, R. M., Yassine, H. M., Mahmoud, K. A., Pintus, G., & Nasrallah, G. K. (2019). Impaired liver size and compromised neurobehavioral activity are elicited by chitosan nanoparticles in the zebrafish embryo model. Nanomaterials, 9(1). https://doi.org/10.3390/nano9010122
Afantitis, A., Melagraki, G., Isigonis, P., Tsoumanis, A., Varsou, D. D., Valsami-Jones, E., Papadiamantis, A., Ellis, L.-J. A., Sarimveis, H., Doganis, P., Karatzas, P., Tsiros, P., Liampa, I., Lobaskin, V., Greco, D., Serra, A., Kinaret, P. A. S., Saarimäki, L. A., Grafström, R., … Lynch, I. (2020). NanoSolveIT Project: Driving nanoinformatics research to develop innovative and integrated tools for in silico nanosafety assessment. Computational and Structural Biotechnology Journal, 18, 583–602. https://doi.org/https://doi.org/10.1016/j.csbj.2020.02.023
Akbarzadeh, A., Rezaei-Sadabady, R., Davaran, S., Joo, S. W., Zarghami, N., Hanifehpour, Y., Samiei, M., Kouhi, M., & Nejati-Koshki, K. (2013). Liposome: classification, preparation, and applications. Nanoscale Research Letters, 8(1), 102. https://doi.org/10.1186/1556-276X-8-102
Amin, M. K., & Boateng, J. S. (2022). Enhancing Stability and Mucoadhesive Properties of Chitosan Nanoparticles by Surface Modification with Sodium Alginate and Polyethylene Glycol for Potential Oral Mucosa Vaccine Delivery. Marine Drugs, 20(3). https://doi.org/10.3390/md20030156
Araldi, R. P., de Melo, T. C., Mendes, T. B., de Sá Júnior, P. L., Nozima, B. H. N., Ito, E. T., de Carvalho, R. F., de Souza, E. B., & de Cassia Stocco, R. (2015). Using the comet and micronucleus assays for genotoxicity studies: A review. Biomedicine & Pharmacotherapy, 72, 74–82. https://doi.org/https://doi.org/10.1016/j.biopha.2015.04.004
Bhattacharya, S., Zhang, Q., Carmichael, P. L., Boekelheide, K., & Andersen, M. E. (2011). Toxicity Testing in the 21st Century: Defining New Risk Assessment Approaches Based on Perturbation of Intracellular Toxicity Pathways. PLOS ONE, 6(6), e20887-. https://doi.org/10.1371/journal.pone.0020887
Blanco, E., Shen, H., & Ferrari, M. (2015). Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology, 33(9), 941–951. https://doi.org/10.1038/nbt.3330
Bozzuto, G., & Molinari, A. (2015). Liposomes as nanomedical devices. In International Journal of Nanomedicine (Vol. 10, pp. 975–999). Dove Medical Press Ltd. https://doi.org/10.2147/IJN.S68861
Bryce, S. M., Shi, J., Nicolette, J., Diehl, M., Sonders, P., Avlasevich, S., Raja, S., Bemis, J. C., & Dertinger, S. D. (2010). High content flow cytometric micronucleus scoring method is applicable to attachment cell lines. Environmental and Molecular Mutagenesis, 51(3), 260–266. https://doi.org/https://doi.org/10.1002/em.20544
Buoso, E., Biundo, F., & Attanzio, A. (2022). New Therapeutic Approaches against Inflammation and Oxidative Stress in Neurodegeneration. Oxidative Medicine and Cellular Longevity, 2022(1), 9824350. https://doi.org/https://doi.org/10.1155/2022/9824350
Cahn, D., & Duncan, G. A. (2022). High-Density Branched PEGylation for Nanoparticle Drug Delivery. Cellular and Molecular Bioengineering, 15(5), 355–366. https://doi.org/10.1007/s12195-022-00727-x
Carriere, M., Sauvaigo, S., Douki, T., & Ravanat, J.-L. (2017). Impact of nanoparticles on DNA repair processes: current knowledge and working hypotheses. Mutagenesis, 32(1), 203–213. https://doi.org/10.1093/mutage/gew052
Chou, C.-M., Mi, F.-L., Horng, J.-L., Lin, L.-Y., Tsai, M.-L., Liu, C.-L., Lu, K.-Y., Chu, C.-Y., Chen, Y.-T., Lee, Y.-L. A., & Cheng, C.-H. (2020). Characterization and toxicology evaluation of low molecular weight chitosan on zebrafish. Carbohydrate Polymers, 240, 116164. https://doi.org/https://doi.org/10.1016/j.carbpol.2020.116164
Cinat, D., Coppes, R. P., & Barazzuol, L. (2021). DNA Damage-Induced Inflammatory Microenvironment and Adult Stem Cell Response. In Frontiers in Cell and Developmental Biology (Vol. 9). Frontiers Media S.A. https://doi.org/10.3389/fcell.2021.729136
Collins, A. R. (2004). The comet assay for DNA damage and repair. Molecular Biotechnology, 26(3), 249–261. https://doi.org/10.1385/MB:26:3:249
Cordelli, E., Bignami, M., & Pacchierotti, F. (2021). Comet assay: a versatile but complex tool in genotoxicity testing. Toxicology Research, 10(1), 68–78. https://doi.org/10.1093/toxres/tfaa093
Din, F. U., Aman, W., Ullah, I., Qureshi, O. S., Mustapha, O., Shafique, S., & Zeb, A. (2017). Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. In International Journal of Nanomedicine (Vol. 12, pp. 7291–7309). Dove Medical Press Ltd. https://doi.org/10.2147/IJN.S146315
Divya, L., Raju, M. B., & Raut, S. Y. (2014). Chitosan-Based Micro and Nanoparticles: A Promising System for Drug Delivery. Research J. Pharm. and Tech, 7(12). www.rjptonline.org
Doak, S. H., & Dusinska, M. (2017). NanoGenotoxicology: present and the future. Mutagenesis, 32(1), 1–4. https://doi.org/10.1093/mutage/gew066
Dusinska, M., Rundén-Pran, E., El Yamani, N., Fjellsbø, L. M., & Collins, A. (2016). Application of the Comet Assay in Nanotoxicology. In D. Anderson & A. Dhawan (Eds.), The Comet Assay in Toxicology (p. 0). The Royal Society of Chemistry. https://doi.org/10.1039/9781782622895-00477
Eastmond, D. A., Hartwig, A., Anderson, D., Anwar, W. A., Cimino, M. C., Dobrev, I., Douglas, G. R., Nohmi, T., Phillips, D. H., & Vickers, C. (2009). Mutagenicity testing for chemical risk assessment: update of the WHO/IPCS Harmonized Scheme. Mutagenesis, 24(4), 341–349. https://doi.org/10.1093/mutage/gep014
Elespuru, R., Pfuhler, S., Aardema, M. J., Chen, T., Doak, S. H., Doherty, A., Farabaugh, C. S., Kenny, J., Manjanatha, M., Mahadevan, B., Moore, M. M., Ouédraogo, G., Stankowski Jr, L. F., & Tanir, J. Y. (2018). Genotoxicity Assessment of Nanomaterials: Recommendations on Best Practices, Assays, and Methods. Toxicological Sciences, 164(2), 391–416. https://doi.org/10.1093/toxsci/kfy100
Elnaggar, Y. S. R., Etman, S. M., Abdelmonsif, D. A., & Abdallah, O. Y. (2015). Intranasal Piperine-Loaded Chitosan Nanoparticles as Brain-Targeted Therapy in Alzheimer’s Disease: Optimization, Biological Efficacy, and Potential Toxicity. Journal of Pharmaceutical Sciences, 104(10), 3544–3556. https://doi.org/10.1002/jps.24557
Elsabahy, M., & Wooley, K. L. (2012). Design of polymeric nanoparticles for biomedical delivery applications. Chem. Soc. Rev., 41(7), 2545–2561. https://doi.org/10.1039/C2CS15327K
Evans, M. D., Dizdaroglu, M., & Cooke, M. S. (2004). Oxidative DNA damage and disease: induction, repair and significance. Mutation Research/Reviews in Mutation Research, 567(1), 1–61. https://doi.org/https://doi.org/10.1016/j.mrrev.2003.11.001
Gajewicz, A., Rasulev, B., Dinadayalane, T. C., Urbaszek, P., Puzyn, T., Leszczynska, D., & Leszczynski, J. (2012). Advancing risk assessment of engineered nanomaterials: Application of computational approaches. Advanced Drug Delivery Reviews, 64(15), 1663–1693. https://doi.org/https://doi.org/10.1016/j.addr.2012.05.014
Gonzalez, L., Sanderson, B. J. S., & Kirsch-Volders, M. (2011). Adaptations of the in vitro MN assay for the genotoxicity assessment of nanomaterials. Mutagenesis, 26(1), 185–191. https://doi.org/10.1093/mutage/geq088
Gupta, A., Eral, H. B., Hatton, T. A., & Doyle, P. S. (2016). Nanoemulsions: Formation, properties and applications. In Soft Matter (Vol. 12, Issue 11, pp. 2826–2841). Royal Society of Chemistry. https://doi.org/10.1039/c5sm02958a
Habas, K., Abdulmwli, M., Demir, E., Jacob, B. K., Najafzadeh, M., & Anderson, D. (2018). DNA damage protection by bulk and nano forms of quercetin in lymphocytes of patients with chronic obstructive pulmonary disease exposed to the food mutagen 2-amino-3-methylimidazo [4,5-f]quinolone (IQ). Environmental Research, 166, 10–15. https://doi.org/https://doi.org/10.1016/j.envres.2018.05.012
Halder, A. K., Melo, A., & Cordeiro, M. N. D. S. (2020). A unified in silico model based on perturbation theory for assessing the genotoxicity of metal oxide nanoparticles. Chemosphere, 244, 125489. https://doi.org/https://doi.org/10.1016/j.chemosphere.2019.125489
Hamouda, R. A., Salman, A. S., Alharbi, A. A., Alhasani, R. H., & Elshamy, M. M. (2021). Assessment of the antigenotoxic effects of alginate and ZnO/alginate–nanocomposites extracted from brown alga fucus vesiculosus in mice. Polymers, 13(21). https://doi.org/10.3390/polym13213839
Honary, S., & Zahir, F. (2013). Effect of zeta potential on the properties of nano-drug delivery systems - A review (Part 2). Tropical Journal of Pharmaceutical Research, 12(2), 265–273. https://doi.org/10.4314/tjpr.v12i2.20
Hu, Y. L., Qi, W., Han, F., Shao, J. Z., & Gao, J. Q. (2011). Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model. International Journal of Nanomedicine, 6, 3351–3359. https://doi.org/10.2147/ijn.s25853
Huo, S., Jin, S., Ma, X., Xue, X., Yang, K., Kumar, A., Wang, P. C., Zhang, J., Hu, Z., & Liang, X.-J. (2014). Ultrasmall Gold Nanoparticles as Carriers for Nucleus-Based Gene Therapy Due to Size-Dependent Nuclear Entry. ACS Nano, 8(6), 5852–5862. https://doi.org/10.1021/nn5008572
Inglut, C. T., Sorrin, A. J., Kuruppu, T., Vig, S., Cicalo, J., Ahmad, H., & Huang, H. C. (2020). Immunological and toxicological considerations for the design of liposomes. In Nanomaterials (Vol. 10, Issue 2). MDPI AG. https://doi.org/10.3390/nano10020190
Iwaoka, S., Nakamura, T., Takano, S., Tsuchiya, S., & Aramaki, Y. (2006). Cationic liposomes induce apoptosis through p38 MAP kinase–caspase-8–Bid pathway in macrophage-like RAW264.7 cells. Journal of Leukocyte Biology, 79(1), 184–191. https://doi.org/10.1189/jlb.0405181
Jokerst, J. V, Lobovkina, T., Zare, R. N., & Gambhir, S. S. (2011). Nanoparticle PEGylation for Imaging and Therapy. Nanomedicine, 6(4), 715–728. https://doi.org/10.2217/nnm.11.19
Kazimirova, A., Baranokova, M., Staruchova, M., Drlickova, M., Volkovova, K., & Dusinska, M. (2019). Titanium dioxide nanoparticles tested for genotoxicity with the comet and micronucleus assays in vitro, ex vivo and in vivo. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 843, 57–65. https://doi.org/https://doi.org/10.1016/j.mrgentox.2019.05.001
Kermanizadeh, A., Gaiser, B. K., Ward, M. B., & Stone, V. (2013). Primary human hepatocytes versus hepatic cell line: assessing their suitability for in vitro nanotoxicology. Nanotoxicology, 7(7), 1255–1271. https://doi.org/10.3109/17435390.2012.734341
Kim, J., Cho, H., Lim, D. K., Joo, M. K., & Kim, K. (2023). Perspectives for Improving the Tumor Targeting of Nanomedicine via the EPR Effect in Clinical Tumors. In International Journal of Molecular Sciences (Vol. 24, Issue 12). MDPI. https://doi.org/10.3390/ijms241210082
Kim, S., Kim, M., Jung, S., Kwon, K., Park, J., Kim, S., Kwon, I., & Tae, G. (2019). Co-delivery of therapeutic protein and catalase-mimic nanoparticle using a biocompatible nanocarrier for enhanced therapeutic effect. Journal of Controlled Release, 309, 181–189. https://doi.org/https://doi.org/10.1016/j.jconrel.2019.07.038
Kirsch-Volders, M., Sofuni, T., Aardema, M., Albertini, S., Eastmond, D., Fenech, M., Ishidate, M., Kirchner, S., Lorge, E., Morita, T., Norppa, H., Surrallés, J., Vanhauwaert, A., & Wakata, A. (2003). Report from the in vitro micronucleus assay working group. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 540(2), 153–163. https://doi.org/https://doi.org/10.1016/j.mrgentox.2003.07.005
Knudsen, K. B., Northeved, H., Kumar EK, P., Permin, A., Gjetting, T., Andresen, T. L., Larsen, S., Wegener, K. M., Lykkesfeldt, J., Jantzen, K., Loft, S., Møller, P., & Roursgaard, M. (2015). In vivo toxicity of cationic micelles and liposomes. Nanomedicine: Nanotechnology, Biology and Medicine, 11(2), 467–477. https://doi.org/https://doi.org/10.1016/j.nano.2014.08.004
Kohl, Y., Rundén-Pran, E., Mariussen, E., Hesler, M., Yamani, N. El, Longhin, E. M., & Dusinska, M. (2020). Genotoxicity of nanomaterials: Advanced in vitro models and high throughput methods for human hazard assessment—a review. In Nanomaterials (Vol. 10, Issue 10, pp. 1–25). MDPI AG. https://doi.org/10.3390/nano10101911
Kumar, P. R., & Vijaya, L. A. (2020). An overview on nanobased drug delivery system. Research Journal of Pharmacy and Technology, 13(10), 4996. https://doi.org/10.5958/0974-360x.2020.00875.6
Kumar, V., Sharma, N., & Maitra, S. S. (2017). In vitro and in vivo toxicity assessment of nanoparticles. International Nano Letters, 7(4), 243–256. https://doi.org/10.1007/s40089-017-0221-3
Kuo, B., Beal, M. A., Wills, J. W., White, P. A., Marchetti, F., Nong, A., Barton-Maclaren, T. S., Houck, K., & Yauk, C. L. (2022). Comprehensive interpretation of in vitro micronucleus test results for 292 chemicals: from hazard identification to risk assessment application. Archives of Toxicology, 96(7), 2067–2085. https://doi.org/10.1007/s00204-022-03286-2
Lewinski, N., Colvin, V., & Drezek, R. (2008). Cytotoxicity of Nanoparticles. Small, 4(1), 26–49. https://doi.org/https://doi.org/10.1002/smll.200700595
Liang, H., Peng, B., Dong, C., Liu, L., Mao, J., Wei, S., Wang, X., Xu, H., Shen, J., Mao, H.-Q., Gao, X., Leong, K. W., & Chen, Y. (2018). Cationic nanoparticle as an inhibitor of cell-free DNA-induced inflammation. Nature Communications, 9(1), 4291. https://doi.org/10.1038/s41467-018-06603-5
Liu, J., Liu, Z., Pang, Y., & Zhou, H. (2022). The interaction between nanoparticles and immune system: application in the treatment of inflammatory diseases. Journal of Nanobiotechnology, 20(1), 127. https://doi.org/10.1186/s12951-022-01343-7
Liu, Q., Sun, M., Wang, T., Zhou, Y., Sun, M., Li, H., Liu, Y., & Xu, A. (2023). The Differential Antagonistic Ability of Curcumin against Cytotoxicity and Genotoxicity Induced by Distinct Heavy Metals. Toxics, 11(3). https://doi.org/10.3390/toxics11030233
Loh, J. W., Yeoh, G., Saunders, M., & Lim, L.-Y. (2010). Uptake and cytotoxicity of chitosan nanoparticles in human liver cells. Toxicology and Applied Pharmacology, 249(2), 148–157. https://doi.org/https://doi.org/10.1016/j.taap.2010.08.029
Lohani, A., Verma, A., Joshi, H., Yadav, N., & Karki, N. (2014). Nanotechnology-Based Cosmeceuticals. International Scholarly Research Notices, 2014(1), 843687. https://doi.org/https://doi.org/10.1155/2014/843687
Lu, H., Zhang, S., Wang, J., & Chen, Q. (2021). A Review on Polymer and Lipid-Based Nanocarriers and Its Application to Nano-Pharmaceutical and Food-Based Systems. In Frontiers in Nutrition (Vol. 8). Frontiers Media S.A. https://doi.org/10.3389/fnut.2021.783831
Lu, X., & Zhang, K. (2018). PEGylation of therapeutic oligonucletides: From linear to highly branched PEG architectures. Nano Research, 11(10), 5519–5534. https://doi.org/10.1007/s12274-018-2131-8
Lu, Y., Liu, Y., & Yang, C. (2017). Evaluating In Vitro DNA Damage Using Comet Assay. JoVE, 128, e56450. https://doi.org/doi:10.3791/56450
Luan, Y., & Honma, M. (2022). Genotoxicity testing and recent advances. Genome Instability & Disease, 3(1), 1–21. https://doi.org/10.1007/s42764-021-00058-7
Ma, T., Arroyo, N., Janot, J. M., Picaud, F., & Balme, S. (2021). Conformation of polyethylene glycol inside confined space: simulation and experimental approaches. Nanomaterials, 11(1), 1–18. https://doi.org/10.3390/nano11010244
Magdolenova, Z., Bilaničová, D., Pojana, G., Fjellsbø, L. M., Hudecova, A., Hasplova, K., Marcomini, A., & Dusinska, M. (2012). Impact of agglomeration and different dispersions of titanium dioxide nanoparticles on the human related in vitro cytotoxicity and genotoxicity. J. Environ. Monit., 14(2), 455–464. https://doi.org/10.1039/C2EM10746E
Magdolenova, Z., Drlickova, M., Henjum, K., Rundén-Pran, E., Tulinska, J., Bilanicova, D., Pojana, G., Kazimirova, A., Barancokova, M., Kuricova, M., Liskova, A., Staruchova, M., Ciampor, F., Vavra, I., Lorenzo, Y., Collins, A., Rinna, A., Fjellsbø, L., Volkovova, K., … Dusinska, M. (2015). Coating-dependent induction of cytotoxicity and genotoxicity of iron oxide nanoparticles. Nanotoxicology, 9(sup1), 44–56. https://doi.org/10.3109/17435390.2013.847505
Maurya, D. K. (2014). HaloJ: An imageJ program for semiautomatic quantification of DNA damage at single-cell level. International Journal of Toxicology, 33(5), 362–366. https://doi.org/10.1177/1091581814549961
Mirakabadi, A. Z., & Moradhaseli, S. (2013). Comparative Cytotoxic Evaluation of Free and Sodium Alginate Nanoparticle-Encapsulated ICD-85 on Primary Lamb Kidney Cells. Iran J Cancer Prev, 6(3), 151–159.
Møller, P., Azqueta, A., Boutet-Robinet, E., Koppen, G., Bonassi, S., Milić, M., Gajski, G., Costa, S., Teixeira, J. P., Costa Pereira, C., Dusinska, M., Godschalk, R., Brunborg, G., Gutzkow, K. B., Giovannelli, L., Cooke, M. S., Richling, E., Laffon, B., Valdiglesias, V., … Langie, S. A. S. (2020). Minimum Information for Reporting on the Comet Assay (MIRCA): recommendations for describing comet assay procedures and results. Nature Protocols, 15(12), 3817–3826. https://doi.org/10.1038/s41596-020-0398-1
Nazarparvar-Noshadi, M., Ezzati Nazhad Dolatabadi, J., Rasoulzadeh, Y., Mohammadian, Y., & Shanehbandi, D. (2020). Apoptosis and DNA damage induced by silica nanoparticles and formaldehyde in human lung epithelial cells. Environmental Science and Pollution Research, 27(15), 18592–18601. https://doi.org/10.1007/s11356-020-08191-8
Omar Zaki, S. S., Katas, H., & Hamid, Z. A. (2015). Lineage-related and particle size-dependent cytotoxicity of chitosan nanoparticles on mouse bone marrow-derived hematopoietic stem and progenitor cells. Food and Chemical Toxicology, 85, 31–44. https://doi.org/https://doi.org/10.1016/j.fct.2015.05.017
Osman IF, Jacob BK, & Anderson D. (2011). Effect of nanoparticles on human cells from healthy individuals and patients with respiratory diseases. J Biomed Nanotechnol, 7(1), 26–27.
Owens, D. E., & Peppas, N. A. (2006). Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. International Journal of Pharmaceutics, 307(1), 93–102. https://doi.org/https://doi.org/10.1016/j.ijpharm.2005.10.010
Paolicelli, P., de la Fuente, M., Sánchez, A., Seijo, B., & Alonso, M. J. (2009). Chitosan nanoparticles for drug delivery to the eye. Expert Opinion on Drug Delivery, 6(3), 239–253. https://doi.org/10.1517/17425240902762818
Parmar, K., Patel, J., & Pathak, Y. (2022). Factors Affecting the Clearance and Biodistribution of Polymeric Nanoparticles. In J. K. Patel & Y. V Pathak (Eds.), Pharmacokinetics and Pharmacodynamics of Nanoparticulate Drug Delivery Systems (pp. 261–272). Springer International Publishing. https://doi.org/10.1007/978-3-030-83395-4_14
Patra, J. K., Das, G., Fraceto, L. F., Campos, E. V. R., Rodriguez-Torres, M. del P., Acosta-Torres, L. S., Diaz-Torres, L. A., Grillo, R., Swamy, M. K., Sharma, S., Habtemariam, S., & Shin, H.-S. (2018). Nano based drug delivery systems: recent developments and future prospects. Journal of Nanobiotechnology, 16(1), 71. https://doi.org/10.1186/s12951-018-0392-8
Pawar, S. N., & Edgar, K. J. (2012). Alginate derivatization: A review of chemistry, properties and applications. Biomaterials, 33(11), 3279–3305. https://doi.org/https://doi.org/10.1016/j.biomaterials.2012.01.007
Prabha, S., Arya, G., Chandra, R., Ahmed, B., & Nimesh, S. (2016). Effect of size on biological properties of nanoparticles employed in gene delivery. In Artificial Cells, Nanomedicine and Biotechnology (Vol. 44, Issue 1, pp. 83–91). Taylor and Francis Ltd. https://doi.org/10.3109/21691401.2014.913054
Preaubert, L., Courbiere, B., Achard, V., Tassistro, V., Greco, F., Orsiere, T., Bottero, J.-Y., Rose, J., Auffan, M., & Perrin, J. (2016). Cerium dioxide nanoparticles affect in vitro fertilization in mice. Nanotoxicology, 10(1), 111–117. https://doi.org/10.3109/17435390.2015.1030792
Rao, J. P., & Geckeler, K. E. (2011). Polymer nanoparticles: Preparation techniques and size-control parameters. Progress in Polymer Science, 36(7), 887–913. https://doi.org/https://doi.org/10.1016/j.progpolymsci.2011.01.001
Rivera Gil, P., Oberdörster, G., Elder, A., Puntes, V., & Parak, W. J. (2010). Correlating Physico-Chemical with Toxicological Properties of Nanoparticles: The Present and the Future. ACS Nano, 4(10), 5527–5531. https://doi.org/10.1021/nn1025687
Sadaqa, E., Utami, R. A., & Mudhakir, D. (2024). In vitro cytotoxic and genotoxic effects of Phyllanthus niruri extract loaded chitosan nanoparticles in TM4 cells and their influence on spermatogenesis. Pharmacia, 71, 1–14. https://doi.org/https://doi.org/10.3897/pharmacia.71.e112138
Sanità, G., Carrese, B., & Lamberti, A. (2020). Nanoparticle Surface Functionalization: How to Improve Biocompatibility and Cellular Internalization. In Frontiers in Molecular Biosciences (Vol. 7). Frontiers Media S.A. https://doi.org/10.3389/fmolb.2020.587012
Saravanan, V., & Tippavajhala, V. K. (2022). Quantum Dots: Targeted and Traceable Drug Delivery System. Research Journal of Pharmacy and Technology, 15(12), 5895–5902. https://doi.org/10.52711/0974-360X.2022.00994
Sercombe, L., Veerati, T., Moheimani, F., Wu, S. Y., Sood, A. K., & Hua, S. (2015). Advances and challenges of liposome assisted drug delivery. In Frontiers in Pharmacology (Vol. 6, Issue DEC). Frontiers Media S.A. https://doi.org/10.3389/fphar.2015.00286
Sestili, P. (2009). The Fast-Halo Assay for the Assessment of DNA Damage at the Single-Cell Level. In S. Vengrova & J. Z. Dalgaard (Eds.), DNA Replication: Methods and Protocols (pp. 517–533). Humana Press. https://doi.org/10.1007/978-1-60327-815-7_30
Sestili, P., Calcabrini, C., Diaz, A. R., Fimognari, C., & Stocchi, V. (2017). The Fast-Halo Assay for the Detection of DNA Damage. In V. V Didenko (Ed.), Fast Detection of DNA Damage: Methods and Protocols (pp. 75–93). Springer New York. https://doi.org/10.1007/978-1-4939-7187-9_6
Sestili, P., Martinelli, C., & Stocchi, V. (2006). The fast halo assay: An improved method to quantify genomic DNA strand breakage at the single-cell level. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 607(2), 205–214. https://doi.org/https://doi.org/10.1016/j.mrgentox.2006.04.018
Shah, V., Taratula, O., Garbuzenko, O. B., Patil, M. L., Savla, R., Zhang, M., & Minko, T. (2013). Genotoxicity of Different Nanocarriers: Possible Modifications for the Delivery of Nucleic Acids. Curr Drug Discov Technol, 10(1), 8–15.
Sharma, V., Anderson, D., & Dhawan, A. (2012). Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2). Apoptosis, 17(8), 852–870. https://doi.org/10.1007/s10495-012-0705-6
Shi, L., Zhang, J., Zhao, M., Tang, S., Cheng, X., Zhang, W., Li, W., Liu, X., Peng, H., & Wang, Q. (2021). Effects of polyethylene glycol on the surface of nanoparticles for targeted drug delivery. Nanoscale, 13(24), 10748–10764. https://doi.org/10.1039/D1NR02065J
Shukla, R. K., Badiye, A., Vajpayee, K., & Kapoor, N. (2021). Genotoxic Potential of Nanoparticles: Structural and Functional Modifications in DNA. In Frontiers in Genetics (Vol. 12). Frontiers Media S.A. https://doi.org/10.3389/fgene.2021.728250
Singh, M. (2021). Assessing Nucleic Acid: CationicCationic Nanoparticle Interaction for Gene DeliveryGene delivery. In K. Narayanan (Ed.), Bio-Carrier Vectors: Methods and Protocols (pp. 43–55). Springer US. https://doi.org/10.1007/978-1-0716-0943-9_4
Singh, N., Manshian, B., Jenkins, G. J. S., Griffiths, S. M., Williams, P. M., Maffeis, T. G. G., Wright, C. J., & Doak, S. H. (2009). NanoGenotoxicology: The DNA damaging potential of engineered nanomaterials. Biomaterials, 30(23), 3891–3914. https://doi.org/https://doi.org/10.1016/j.biomaterials.2009.04.009
Singhal, A., Morris, V. B., Labhasetwar, V., & Ghorpade, A. (2013). Nanoparticle-mediated catalase delivery protects human neurons from oxidative stress. Cell Death and Disease, 4(11). https://doi.org/10.1038/cddis.2013.362
Sommer, S., Buraczewska, I., & Kruszewski, M. (2020). Micronucleus assay: The state of art, and future directions. In International Journal of Molecular Sciences (Vol. 21, Issue 4). MDPI AG. https://doi.org/10.3390/ijms21041534
Spadari, C. de C., de Bastiani, F. W. M. da S., Lopes, L. B., & Ishida, K. (2019). Alginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis. International Journal of Nanomedicine, 14, 5187–5199. https://doi.org/10.2147/IJN.S205350
Suk, J. S., Xu, Q., Kim, N., Hanes, J., & Ensign, L. M. (2016). PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Advanced Drug Delivery Reviews, 99, 28–51. https://doi.org/https://doi.org/10.1016/j.addr.2015.09.012
Thai, H., Thuy Nguyen, C., Thi Thach, L., Thi Tran, M., Duc Mai, H., Thi Thu Nguyen, T., Duc Le, G., Van Can, M., Dai Tran, L., Long Bach, G., Ramadass, K., Sathish, C. I., & Van Le, Q. (2020). Characterization of chitosan/alginate/lovastatin nanoparticles and investigation of their toxic effects in vitro and in vivo. Scientific Reports, 10(1), 909. https://doi.org/10.1038/s41598-020-57666-8
Thomas, D., & Latha, M. S. (2023). Alginate Based Nanocarriers for Controlled Drug Delivery Applications. In S. Jana & S. Jana (Eds.), Alginate Biomaterial: Drug Delivery Strategies and Biomedical Engineering (pp. 61–83). Springer Nature Singapore. https://doi.org/10.1007/978-981-19-6937-9_3
Tirichen, H., Yaigoub, H., Xu, W., Wu, C., Li, R., & Li, Y. (2021). Mitochondrial Reactive Oxygen Species and Their Contribution in Chronic Kidney Disease Progression Through Oxidative Stress. In Frontiers in Physiology (Vol. 12). Frontiers Media S.A. https://doi.org/10.3389/fphys.2021.627837
Tønnesen, H. H., & Karlsen, J. (2002). Alginate in Drug Delivery Systems. Drug Development and Industrial Pharmacy, 28(6), 621–630. https://doi.org/10.1081/DDC-120003853
Van Haute, D., Liu, A. T., & Berlin, J. M. (2018). Coating Metal Nanoparticle Surfaces with Small Organic Molecules Can Reduce Nonspecific Cell Uptake. ACS Nano, 12(1), 117–127. https://doi.org/10.1021/acsnano.7b03025
Vidya, G., Gladwin, V., & Chand, P. (2015). A comprehensive review on clinical applications of comet assay. In Journal of Clinical and Diagnostic Research (Vol. 9, Issue 3, pp. GE01–GE05). Journal of Clinical and Diagnostic Research. https://doi.org/10.7860/JCDR/2015/12062.5622
Wang, Y., Zhou, J., Liu, L., Huang, C., Zhou, D., & Fu, L. (2016). Characterization and toxicology evaluation of chitosan nanoparticles on the embryonic development of zebrafish, Danio rerio. Carbohydrate Polymers, 141, 204–210. https://doi.org/https://doi.org/10.1016/j.carbpol.2016.01.012
Ways, T. M. M., Lau, W. M., & Khutoryanskiy, V. V. (2018). Chitosan and its derivatives for application in mucoadhesive drug delivery systems. In Polymers (Vol. 10, Issue 3). MDPI AG. https://doi.org/10.3390/polym10030267
Xie, D., Hu, J., Yang, Z., Wu, T., Xu, W., Meng, Q., Cao, K., & Luo, X. (2022). Vitamin Supplementation Protects against Nanomaterial-Induced Oxidative Stress and Inflammation Damages: A Meta-Analysis of In Vitro and In Vivo Studies. Nutrients, 14. https://api.semanticscholar.org/CorpusID:249217931
Ye, L., Kollie, L., Liu, X., Guo, W., Ying, X., Zhu, J., Yang, S., & Yu, M. (2021). Antitumor activity and potential mechanism of novel fullerene derivative nanoparticles. In Molecules (Vol. 26, Issue 11). MDPI AG. https://doi.org/10.3390/molecules26113252
Ye, Z., Shi, Y., Lees-Miller, S. P., & Tainer, J. A. (2021). Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy. In Frontiers in Immunology (Vol. 12). Frontiers Media S.A. https://doi.org/10.3389/fimmu.2021.797880
Yu, Z., Li, Q., Wang, J., Yu, Y., Wang, Y., Zhou, Q., & Li, P. (2020). Reactive Oxygen Species-Related Nanoparticle Toxicity in the Biomedical Field. Nanoscale Research Letters, 15(1), 115. https://doi.org/10.1186/s11671-020-03344-7
Yuan, Z., Li, Y., Hu, Y., You, J., Higashisaka, K., Nagano, K., Tsutsumi, Y., & Gao, J. (2016). Chitosan nanoparticles and their Tween 80 modified counterparts disrupt the developmental profile of zebrafish embryos. International Journal of Pharmaceutics, 515(1), 644–656. https://doi.org/https://doi.org/10.1016/j.ijpharm.2016.10.071
Zhanataev, A. K., Anisina, E. A., Kulakova, A. V, Shilovskiy, I. P., Lisitsyn, A. A., Koloskova, O. O., Khaitov, M. R., & Durnev, A. D. (2020). Genotoxicity of cationic lipopeptide nanoparticles. Toxicology Letters, 328, 1–6. https://doi.org/https://doi.org/10.1016/j.toxlet.2020.04.011
Zielińska, A., Costa, B., Ferreira, M. V., Miguéis, D., Louros, J. M. S., Durazzo, A., Lucarini, M., Eder, P., Chaud, M. V., Morsink, M., Willemen, N., Severino, P., Santini, A., & Souto, E. B. (2020). Nanotoxicology and nanosafety: Safety-by-design and testing at a glance. In International Journal of Environmental Research and Public Health (Vol. 17, Issue 13, pp. 1–22). MDPI AG. https://doi.org/10.3390/ijerph17134657
Zohri, M., Arefian, E., Akbari Javar, H., Gazori, T., Aghaee-Bakhtiari, S. H., Taheri, M., Fatahi, Y., Azadi, A., Khoshayand, M. R., & Ghahremani, M. H. (2021). Potential of chitosan/alginate nanoparticles as a non-viral vector for gene delivery: Formulation and optimization using D-optimal design. Materials Science and Engineering: C, 128, 112262. https://doi.org/https://doi.org/10.1016/j.msec.2021.112262
Published
2024-12-31
How to Cite
Sadaqa, E., Setiawansyah, A., Nugroho, B. H., Hidayati, N., & Arsul, M. I. (2024). Organic Nanoparticle Genotoxicity: Current Understanding and Future Testing Needs. Ad-Dawaa’ Journal of Pharmaceutical Sciences, 7(2), 77-102. https://doi.org/10.24252/djps.v7i2.52943
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