Abstract
The expanding horizon of nanotechnology has covered most of the parts of our life including general household items to drug delivery and therapeutics. The progresses made in the nanotechnology field provided us some of the clinically useful nano-based products apart from the more than 50 products in pipeline. However, as these products are intended for human use, they also raise some critical safety concerns primarily due to their altered physicochemical properties different from the bulk. Further, the use of nanocarriers has also been found to be associated with different unwanted toxicological observations which depends on different factors. Hence, the safe and efficacious use of these nanocarriers strictly entails the comprehensive and thorough knowledge of the toxicological potential of nanocarriers. Further, the harmonious integration of academia, researcher, industries and regulatory bodies is warranted to ensure the proper regulation of their use.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin cardiomyopathy. Cardiology. 2010;115:155–62.
Saifi MA, Khan W, Godugu C. Cytotoxicity of nanomaterials: using nanotoxicology to address the safety concerns of nanoparticles. Pharm Nanotechnol. 2018;6:3–16.
Saifi MA, Khurana A, Godugu C. Nanotoxicology: toxicity and risk assessment of nanomaterials. In: Nanomaterials in chromatography: Elsevier; 2018. p. 437–65.
Buchman JT, Hudson-Smith NV, Landy KM, Haynes CL. Understanding nanoparticle toxicity mechanisms to inform redesign strategies to reduce environmental impact. Acc Chem Res. 2019;52:1632.
Asare N, et al. Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells. Toxicology. 2012;291:65–72.
Eom H-J, Choi J. p38 MAPK activation, DNA damage, cell cycle arrest and apoptosis as mechanisms of toxicity of silver nanoparticles in Jurkat T cells. Environ Sci Technol. 2010;44:8337–42.
Chueh PJ, Liang R-Y, Lee Y-H, Zeng Z-M, Chuang S-M. Differential cytotoxic effects of gold nanoparticles in different mammalian cell lines. J Hazard Mater. 2014;264:303–12.
Cui W, et al. Effects of aggregation and the surface properties of gold nanoparticles on cytotoxicity and cell growth. Nanomedicine. 2012;8:46–53.
Coradeghini R, et al. Size-dependent toxicity and cell interaction mechanisms of gold nanoparticles on mouse fibroblasts. Toxicol Lett. 2013;217:205–16.
Jia G, et al. Cytotoxicity of carbon nanomaterials: single-wall nanotube, multi-wall nanotube, and fullerene. Environ Sci Technol. 2005;39:1378–83.
Lin J, Zhang H, Chen Z, Zheng Y. Penetration of lipid membranes by gold nanoparticles: insights into cellular uptake, cytotoxicity, and their relationship. ACS Nano. 2010;4:5421–9.
Voinov MA, Pagán JOS, Morrison E, Smirnova TI, Smirnov AI. Surface-mediated production of hydroxyl radicals as a mechanism of iron oxide nanoparticle biotoxicity. J Am Chem Soc. 2010;133:35–41.
Sun L, et al. Cytotoxicity and mitochondrial damage caused by silica nanoparticles. Toxicol In Vitro. 2011;25:1619–29.
Athinarayanan J, Periasamy VS, Alsaif MA, Al-Warthan AA, Alshatwi AA. Presence of nanosilica (E551) in commercial food products: TNF-mediated oxidative stress and altered cell cycle progression in human lung fibroblast cells. Cell Biol Toxicol. 2014;30:89–100.
Shi J, et al. Microsomal glutathione transferase 1 protects against toxicity induced by silica nanoparticles but not by zinc oxide nanoparticles. ACS Nano. 2012;6:1925–38.
Vandebriel RJ, De Jong WH. A review of mammalian toxicity of ZnO nanoparticles. Nanotechnol Sci Appl. 2012;5:61.
Li JJ, et al. Gold nanoparticles induce oxidative damage in lung fibroblasts in vitro. Adv Mater. 2008;20:138–42.
Ahamed M, et al. DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells. Toxicol Appl Pharmacol. 2008;233:404–10.
Dufour EK, Kumaravel T, Nohynek GJ, Kirkland D, Toutain H. Clastogenicity, photo-clastogenicity or pseudo-photo-clastogenicity: genotoxic effects of zinc oxide in the dark, in pre-irradiated or simultaneously irradiated Chinese hamster ovary cells. Mutat Res Toxicol Environ Mutagen. 2006;607:215–24.
Sadeghiani N, et al. Genotoxicity and inflammatory investigation in mice treated with magnetite nanoparticles surface coated with polyaspartic acid. J Magn Magn Mater. 2005;289:466–8.
Zhu S, Oberdörster E, Haasch ML. Toxicity of an engineered nanoparticle (fullerene, C60) in two aquatic species Daphnia and fathead minnow. Mar Environ Res. 2006;62:S5–9.
Lovern SB, Klaper R. Daphnia magna mortality when exposed to titanium dioxide and fullerene (C60) nanoparticles. Environ Toxicol Chem. 2006;25:1132–7.
Mohammed Sadiq I, Chandrasekaran N, Mukherjee A. Studies on effect of TiO2 nanoparticles on growth and membrane permeability of Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis. Curr Nanosci. 2010;6:381–7.
**u Z, Zhang Q, Puppala HL, Colvin VL, Alvarez PJJ. Negligible particle-specific antibacterial activity of silver nanoparticles. Nano Lett. 2012;12:4271–5.
Li Y, Zhang W, Niu J, Chen Y. Mechanism of photogenerated reactive oxygen species and correlation with the antibacterial properties of engineered metal-oxide nanoparticles. ACS Nano. 2012;6:5164–73.
Hund-Rinke K, Simon M. Ecotoxic effect of photocatalytic active nanoparticles (TiO2) on algae and daphnids (8 pp). Environ Sci Pollut Res. 2006;13:225–32.
Navarro E, et al. Environmental behavior and ecotoxicity of engineered nanoparticles to algae, plants, and fungi. Ecotoxicology. 2008;17:372–86.
Maurer-Jones MA, Gunsolus IL, Murphy CJ, Haynes CL. Toxicity of engineered nanoparticles in the environment. Anal Chem. 2013;85:3036–49.
Singh RP, Ramarao P. Accumulated polymer degradation products as effector molecules in cytotoxicity of polymeric nanoparticles. Toxicol Sci. 2013;136:131–43.
Pan Y, et al. Size-dependent cytotoxicity of gold nanoparticles. Small. 2007;3:1941–9.
Adams CP, Walker KA, Obare SO, Docherty KM. Size-dependent antimicrobial effects of novel palladium nanoparticles. PLoS One. 2014;9:e85981.
Ivask A, et al. Size-dependent toxicity of silver nanoparticles to bacteria, yeast, algae, crustaceans and mammalian cells in vitro. PLoS One. 2014;9:e102108.
Kang S, Herzberg M, Rodrigues DF, Elimelech M. Antibacterial effects of carbon nanotubes: size does matter! Langmuir. 2008;24:6409–13.
Kim I-Y, Joachim E, Choi H, Kim K. Toxicity of silica nanoparticles depends on size, dose, and cell type. Nanomedicine. 2015;11:1407–16.
Park KH, Chhowalla M, Iqbal Z, Sesti F. Single-walled carbon nanotubes are a new class of ion channel blockers. J Biol Chem. 2003;278:50212–6.
Lee JH, et al. Rod-shaped iron oxide nanoparticles are more toxic than sphere-shaped nanoparticles to murine macrophage cells. Environ Toxicol Chem. 2014;33:2759–66.
Stoehr LC, et al. Shape matters: effects of silver nanospheres and wires on human alveolar epithelial cells. Part Fibre Toxicol. 2011;8:36.
Heng BC, et al. Evaluation of the cytotoxic and inflammatory potential of differentially shaped zinc oxide nanoparticles. Arch Toxicol. 2011;85:1517–28.
Takahashi H, et al. Modification of gold nanorods using phosphatidylcholine to reduce cytotoxicity. Langmuir. 2006;22:2–5.
Yang H, Liu C, Yang D, Zhang H, ** Z. Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: the role of particle size, shape and composition. J Appl Toxicol. 2009;29:69–78.
Firme CP III, Bandaru PR. Toxicity issues in the application of carbon nanotubes to biological systems. Nanomedicine. 2010;6:245–56.
Ruge CA, et al. Uptake of nanoparticles by alveolar macrophages is triggered by surfactant protein A. Nanomedicine. 2011;7:690–3.
Ge C, et al. Binding of blood proteins to carbon nanotubes reduces cytotoxicity. Proc Natl Acad Sci. 2011;108:16968–73.
Hu W, et al. Protein corona-mediated mitigation of cytotoxicity of graphene oxide. ACS Nano. 2011;5:3693–700.
Panas A, et al. Screening of different metal oxide nanoparticles reveals selective toxicity and inflammatory potential of silica nanoparticles in lung epithelial cells and macrophages. Nanotoxicology. 2012;7:259–73.
Sayes CM, et al. Functionalization density dependence of single-walled carbon nanotubes cytotoxicity in vitro. Toxicol Lett. 2006;161:135–42.
Moghimi SM, et al. A two-stage poly (ethylenimine)-mediated cytotoxicity: implications for gene transfer/therapy. Mol Ther. 2005;11:990–5.
Lim D, et al. Oxidative stress-related PMK-1 P38 MAPK activation as a mechanism for toxicity of silver nanoparticles to reproduction in the nematode Caenorhabditis elegans. Environ Toxicol Chem. 2012;31:585–92.
Liu X, Sun J. Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-κB pathways. Biomaterials. 2010;31:8198–209.
Ryman-Rasmussen JP, et al. Inhaled multiwalled carbon nanotubes potentiate airway fibrosis in murine allergic asthma. Am J Respir Cell Mol Biol. 2009;40:349–58.
Porter DW, et al. Mouse pulmonary dose-and time course-responses induced by exposure to multi-walled carbon nanotubes. Toxicology. 2010;269:136–47.
Shvedova AA, et al. Vitamin E deficiency enhances pulmonary inflammatory response and oxidative stress induced by single-walled carbon nanotubes in C57BL/6 mice. Toxicol Appl Pharmacol. 2007;221:339–48.
Wilhelmi V, et al. Evaluation of apoptosis induced by nanoparticles and fine particles in RAW 264.7 macrophages: facts and artefacts. Toxicol In Vitro. 2012;26:323–34.
Khlebtsov N, Dykman L. Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies. Chem Soc Rev. 2011;40:1647–71.
Elsaesser A, Howard CV. Toxicology of nanoparticles. Adv Drug Deliv Rev. 2012;64:129–37.
Sharma HS, Sharma A. Nanoparticles aggravate heat stress induced cognitive deficits, blood–brain barrier disruption, edema formation and brain pathology. Prog Brain Res. 2007;162:245–73.
Ma L, et al. Oxidative stress in the brain of mice caused by translocated nanoparticulate TiO2 delivered to the abdominal cavity. Biomaterials. 2010;31:99–105.
Buerki-Thurnherr T, von Mandach U, Wick P. Knocking at the door of the unborn child: engineered nanoparticles at the human placental barrier. Swiss Med Wkly. 2012;142:w13559.
Hougaard KS, et al. A perspective on the developmental toxicity of inhaled nanoparticles. Reprod Toxicol. 2015;56:118–40.
Hougaard KS, et al. Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-titan). A study in mice. Part Fibre Toxicol. 2010;7:16.
Shimizu M, et al. Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse. Part Fibre Toxicol. 2009;6:20.
Yamashita K, et al. Silica and titanium dioxide nanoparticles cause pregnancy complications in mice. Nat Nanotechnol. 2011;6:321.
Campagnolo L, et al. Biodistribution and toxicity of pegylated single wall carbon nanotubes in pregnant mice. Part Fibre Toxicol. 2013;10:21.
Rattanapinyopituk K, et al. Demonstration of the clathrin-and caveolin-mediated endocytosis at the maternal–fetal barrier in mouse placenta after intravenous administration of gold nanoparticles. J Vet Med Sci. 2013:13–512.
Park E-J, et al. Repeated-dose toxicity and inflammatory responses in mice by oral administration of silver nanoparticles. Environ Toxicol Pharmacol. 2010;30:162–8.
Bai Y, et al. Repeated administrations of carbon nanotubes in male mice cause reversible testis damage without affecting fertility. Nat Nanotechnol. 2010;5:683.
Lan Z, Yang W-X. Nanoparticles and spermatogenesis: how do nanoparticles affect spermatogenesis and penetrate the blood–testis barrier. Nanomedicine. 2012;7:579–96.
Brannon-Peppas L, Blanchette JO. Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev. 2004;56:1649–59.
Xu Y-Y, et al. Intravenous administration of multiwalled carbon nanotubes aggravates high-fat diet-induced nonalcoholic steatohepatitis in Sprague Dawley rats. Int J Toxicol. 2016;35:634–43.
Senior JH. Fate and behavior of liposomes in vivo: a review of controlling factors. Crit Rev Ther Drug Carrier Syst. 1987;3:123–93.
Jain S, et al. Toxicity of multiwalled carbon nanotubes with end defects critically depends on their functionalization density. Chem Res Toxicol. 2011;24:2028–39.
Suk JS, Xu Q, Kim N, Hanes J, Ensign LM. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev. 2016;99:28–51.
Eliyahu H, Servel N, Domb AJ, Barenholz Y. Lipoplex-induced hemagglutination: potential involvement in intravenous gene delivery. Gene Ther. 2002;9:850.
Qi R, et al. PEG-conjugated PAMAM dendrimers mediate efficient intramuscular gene expression. AAPS J. 2009;11:395.
Gabizon AA, et al. Reduced toxicity and superior therapeutic activity of a mitomycin C lipid-based prodrug incorporated in pegylated liposomes. Clin Cancer Res. 2006;12:1913–20.
Luo M, et al. Reducing ZnO nanoparticle cytotoxicity by surface modification. Nanoscale. 2014;6:5791–8.
Lankoff A, et al. Effect of surface modification of silica nanoparticles on toxicity and cellular uptake by human peripheral blood lymphocytes in vitro. Nanotoxicology. 2012;7:235–50.
Yung MMN, et al. Physicochemical characteristics and toxicity of surface-modified zinc oxide nanoparticles to freshwater and marine microalgae. Sci Rep. 2017;7:15909.
** yields nanoparticles with reduced toxicity in the rodent lung and zebrafish embryos. ACS Nano. 2011;5:1223–35.
Nie Z, et al. Enhanced radical scavenging activity by antioxidant-functionalized gold nanoparticles: a novel inspiration for development of new artificial antioxidants. Free Radic Biol Med. 2007;43:1243–54.
Khurana A, Tekula S, Saifi MA, Venkatesh P, Godugu C. Therapeutic applications of selenium nanoparticles. Biomed Pharmacother. 2019;111:802–12.
Sangomla S, Saifi MA, Khurana A, Godugu C. Nanoceria ameliorates doxorubicin induced cardiotoxicity: possible mitigation via reduction of oxidative stress and inflammation. J Trace Elem Med Biol. 2018;47:53–62.
Khurana A, et al. Yttrium oxide nanoparticles reduce the severity of acute pancreatitis caused by cerulein hyperstimulation. Nanomedicine. 2019;18:54–65.
Singh RP, Ramarao P. Cellular uptake, intracellular trafficking and cytotoxicity of silver nanoparticles. Toxicol Lett. 2012;213:249–59.
Wang H, Wu L, Reinhard BM. Scavenger receptor mediated endocytosis of silver nanoparticles into J774A. 1 macrophages is heterogeneous. ACS Nano. 2012;6:7122–32.
Wang X, et al. Multi-walled carbon nanotubes induce apoptosis via mitochondrial pathway and scavenger receptor. Toxicol In Vitro. 2012;26:799–806.
Shannahan JH, et al. Formation of a protein corona on silver nanoparticles mediates cellular toxicity via scavenger receptors. Toxicol Sci. 2014;143:136–46.
Shannahan JH, Bai W, Brown JM. Implications of scavenger receptors in the safe development of nanotherapeutics. Receptors Clin Investig. 2015;2:e811.
Orr GA, et al. Cellular recognition and trafficking of amorphous silica nanoparticles by macrophage scavenger receptor a. Nanotoxicology. 2011;5:296–311.
Wörle-Knirsch JM, Pulskamp K, Krug HF. Oops they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Lett. 2006;6:1261–8.
Angius F, Floris A. Liposomes and MTT cell viability assay: an incompatible affair. Toxicol In Vitro. 2015;29:314–9.
Guo L, et al. Adsorption of essential micronutrients by carbon nanotubes and the implications for nanotoxicity testing. Small. 2008;4:721–7.
Adams LK, Lyon DY, Alvarez PJJ. Comparative eco-toxicity of nanoscale TiO2, SiO2, and ZnO water suspensions. Water Res. 2006;40:3527–32.
Fröhlich E. Role of omics techniques in the toxicity testing of nanoparticles. J Nanobiotechnol. 2017;15:84.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Saifi, M.A., Poduri, R., Godugu, C. (2021). Nanomedicine: Implications of Nanotoxicology. In: Poduri, R. (eds) Drug Discovery and Development. Springer, Singapore. https://doi.org/10.1007/978-981-15-5534-3_13
Download citation
DOI: https://doi.org/10.1007/978-981-15-5534-3_13
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-5533-6
Online ISBN: 978-981-15-5534-3
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)