1932

Abstract

Nanoparticles from natural and anthropogenic sources are abundant in the environment, thus human exposure to nanoparticles is inevitable. Due to this constant exposure, it is critically important to understand the potential acute and chronic adverse effects that nanoparticles may cause to humans. In this review, we explore and highlight the current state of nanotoxicology research with a focus on mechanistic understanding of nanoparticle toxicity at organ, tissue, cell, and biomolecular levels. We discuss nanotoxicity mechanisms, including generation of reactive oxygen species, nanoparticle disintegration, modulation of cell signaling pathways, protein corona formation, and poly(ethylene glycol)-mediated immunogenicity. We conclude with a perspective on potential approaches to advance current understanding of nanoparticle toxicity. Such improved understanding may lead to mitigation strategies that could enable safe application of nanoparticles in humans. Advances in nanotoxicity research will ultimately inform efforts to establish standardized regulatory frameworks with the goal of fully exploiting the potential of nanotechnology while minimizing harm to humans.

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2021-01-06
2024-04-20
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Literature Cited

  1. 1. 
    Br. Stand. Inst. 2007. Terminology for nanomaterials Publicly Availab. Specif., Br. Stand. Inst. London:
  2. 2. 
    Li N, Georas S, Alexis N, Fritz P, Xia T et al. 2016. A work group report on ultrafine particles (American Academy of Allergy, Asthma & Immunology): why ambient ultrafine and engineered nanoparticles should receive special attention for possible adverse health outcomes in human subjects. J. Allergy Clin. Immunol. 138:2386–96
    [Google Scholar]
  3. 3. 
    Santos AC, Morais F, Simões A, Pereira I, Sequeira JAD et al. 2019. Nanotechnology for the development of new cosmetic formulations. Expert Opin. Drug Deliv. 16:4313–30
    [Google Scholar]
  4. 4. 
    Hajba L, Guttman A. 2016. The use of magnetic nanoparticles in cancer theranostics: toward handheld diagnostic devices. Biotechnol. Adv. 34:4354–61
    [Google Scholar]
  5. 5. 
    Liu Y, Bhattarai P, Dai Z, Chen X 2019. Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer. Chem. Soc. Rev. 48:72053–108
    [Google Scholar]
  6. 6. 
    Hochella MF, Mogk DW, Ranville J, Allen IC, Luther GW et al. 2019. Natural, incidental, and engineered nanomaterials and their impacts on the Earth system. Science 363:6434eaau8299
    [Google Scholar]
  7. 7. 
    Mills NL, Miller MR, Lucking AJ, Beveridge J, Flint L et al. 2011. Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation. Eur. Heart J. 32:212660–71
    [Google Scholar]
  8. 8. 
    Narum SM, Le T, Le DP, Lee JC, Donahue ND et al. 2020. Passive targeting in nanomedicine: fundamental concepts, body interactions, and clinical potential. Nanoparticles for Biomedical Applications EJ Chung, L Leon, C Rinaldi 37–53 Amsterdam: Elsevier
    [Google Scholar]
  9. 9. 
    Sindhwani S, Syed AM, Ngai J, Kingston BR, Maiorino L et al. 2020. The entry of nanoparticles into solid tumours. Nat. Mater. 19:566–75
    [Google Scholar]
  10. 10. 
    Mohammed YH, Holmes A, Haridass IN, Sanchez WY, Studier H et al. 2019. Support for the safe use of zinc oxide nanoparticle sunscreens: lack of skin penetration or cellular toxicity after repeated application in volunteers. J. Investig. Dermatol. 139:2308–15
    [Google Scholar]
  11. 11. 
    Albanese A, Tang PS, Chan WCW 2012. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu. Rev. Biomed. Eng. 14:1–16
    [Google Scholar]
  12. 12. 
    Elsaesser A, Howard CV. 2012. Toxicology of nanoparticles. Adv. Drug Deliv. Rev. 64:2129–37
    [Google Scholar]
  13. 13. 
    Muhr V, Wilhelm S, Hirsch T, Wolfbeis OS 2014. Upconversion nanoparticles: from hydrophobic to hydrophilic surfaces. Acc. Chem. Res. 47:123481–93
    [Google Scholar]
  14. 14. 
    Elci SG, Jiang Y, Yan B, Kim ST, Saha K et al. 2016. Surface charge controls the suborgan biodistributions of gold nanoparticles. ACS Nano 10:55536–42
    [Google Scholar]
  15. 15. 
    Poon W, Zhang Y-N, Ouyang B, Kingston BR, Wu JLY et al. 2019. Elimination pathways of nanoparticles. ACS Nano 13:55785–98
    [Google Scholar]
  16. 16. 
    Liu J, Feng X, Wei L, Chen L, Song B, Shao L 2016. The toxicology of ion-shedding zinc oxide nanoparticles. Crit. Rev. Toxicol. 46:4348–84
    [Google Scholar]
  17. 17. 
    Sun D, Zhang W, Mou Z, Chen Y, Guo F et al. 2017. Transcriptome analysis reveals silver nanoparticle-decorated quercetin antibacterial molecular mechanism. ACS Appl. Mater Interfaces 9:1110047–60
    [Google Scholar]
  18. 18. 
    El-Rafie HM, Hamed MA-A. 2014. Antioxidant and anti-inflammatory activities of silver nanoparticles biosynthesized from aqueous leaves extracts of four Terminalia species. Adv. Nat. Sci. Nanosci. Nanotechnol. 5:3035008
    [Google Scholar]
  19. 19. 
    Holmes AM, Song Z, Moghimi HR, Roberts MS 2016. Relative penetration of zinc oxide and zinc ions into human skin after application of different zinc oxide formulations. ACS Nano 10:21810–19
    [Google Scholar]
  20. 20. 
    Rivera Gil P, Oberdörster G, Elder A, Puntes V, Parak WJ 2010. Correlating physico-chemical with toxicological properties of nanoparticles: the present and the future. ACS Nano 4:105527–31
    [Google Scholar]
  21. 21. 
    Donahue ND, Acar H, Wilhelm S 2019. Concepts of nanoparticle cellular uptake, intracellular trafficking, and kinetics in nanomedicine. Adv. Drug Deliv. Rev. 143:68–96
    [Google Scholar]
  22. 22. 
    Pan Y, Neuss S, Leifert A, Fischler M, Wen F et al. 2007. Size-dependent cytotoxicity of gold nanoparticles. Small 3:111941–49
    [Google Scholar]
  23. 23. 
    Bozich JS, Lohse SE, Torelli MD, Murphy CJ, Hamers RJ, Klaper RD 2014. Surface chemistry, charge and ligand type impact the toxicity of gold nanoparticles to Daphnia magna. . Environ. Sci.: Nano 1:3260–70
    [Google Scholar]
  24. 24. 
    Lee JC, Donahue ND, Mao AS, Karim A, Komarneni M et al. 2020. Exploring maleimide-based nanoparticle surface engineering to control cellular interactions. ACS Appl. Nano Mater. 3:2421–29
    [Google Scholar]
  25. 25. 
    Fröhlich E. 2012. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int. J. Nanomed. 7:5577–91
    [Google Scholar]
  26. 26. 
    Sukhanova A, Bozrova S, Sokolov P, Berestovoy M, Karaulov A, Nabiev I 2018. Dependence of nanoparticle toxicity on their physical and chemical properties. Nanoscale Res. Lett. 13:144
    [Google Scholar]
  27. 27. 
    Tripathy N, Hong T-K, Ha K-T, Jeong H-S, Hahn Y-B 2014. Effect of ZnO nanoparticles aggregation on the toxicity in RAW 264.7 murine macrophage. J. Hazard. Mater. 270:110–17
    [Google Scholar]
  28. 28. 
    Albanese A, Chan WCW. 2011. Effect of gold nanoparticle aggregation on cell uptake and toxicity. ACS Nano 5:75478–89
    [Google Scholar]
  29. 29. 
    Zhao X, Ng S, Heng BC, Guo J, Ma L et al. 2013. Cytotoxicity of hydroxyapatite nanoparticles is shape and cell dependent. Arch. Toxicol. 87:61037–52
    [Google Scholar]
  30. 30. 
    Wang J, Chen H-J, Hang T, Yu Y, Liu G et al. 2018. Physical activation of innate immunity by spiky particles. Nat. Nanotechnol. 13:111078–86
    [Google Scholar]
  31. 31. 
    Dai Q, Wilhelm S, Ding D, Syed AM, Sindhwani S et al. 2018. Quantifying the ligand-coated nanoparticle delivery to cancer cells in solid tumors. ACS Nano 12:88423–35
    [Google Scholar]
  32. 32. 
    Wilhelm S, Tavares AJ, Dai Q, Ohta S, Audet J et al. 2016. Analysis of nanoparticle delivery to tumours. Nat. Rev. Mater. 1:516014
    [Google Scholar]
  33. 33. 
    Tsoi KM, MacParland SA, Ma X-Z, Spetzler VN, Echeverri J et al. 2016. Mechanism of hard-nanomaterial clearance by the liver. Nat. Mater. 15:111212–21
    [Google Scholar]
  34. 34. 
    Du B, Yu M, Zheng J 2018. Transport and interactions of nanoparticles in the kidneys. Nat. Rev. Mater. 3:10358–74
    [Google Scholar]
  35. 35. 
    Tahover E, Patil YP, Gabizon AA 2015. Emerging delivery systems to reduce doxorubicin cardiotoxicity and improve therapeutic index: focus on liposomes. Anticancer Drugs 26:3241–58
    [Google Scholar]
  36. 36. 
    Westerhoff P, Atkinson A, Fortner J, Wong MS, Zimmerman J et al. 2018. Low risk posed by engineered and incidental nanoparticles in drinking water. Nat. Nanotechnol. 13:8661–69
    [Google Scholar]
  37. 37. 
    Zhu S, Gong L, Li Y, Xu H, Gu Z, Zhao Y 2019. Safety assessment of nanomaterials to eyes: an important but neglected issue. Adv. Sci. 6:161802289
    [Google Scholar]
  38. 38. 
    Liou S-H, Tsou T-C, Wang S-L, Li L-A, Chiang H-C et al. 2012. Epidemiological study of health hazards among workers handling engineered nanomaterials. J. Nanopart. Res. 14:8878
    [Google Scholar]
  39. 39. 
    Ye L, Yong K-T, Liu L, Roy I, Hu R et al. 2012. A pilot study in non-human primates shows no adverse response to intravenous injection of quantum dots. Nat. Nanotechnol. 7:7453–58
    [Google Scholar]
  40. 40. 
    Qiao H, Liu W, Gu H, Wang D, Wang Y 2015. The transport and deposition of nanoparticles in respiratory system by inhalation. J. Nanomater. 2015:394507
    [Google Scholar]
  41. 41. 
    Zhang H, Ji Z, Xia T, Meng H, Low-Kam C et al. 2012. Use of metal oxide nanoparticle band gap to develop a predictive paradigm for oxidative stress and acute pulmonary inflammation. ACS Nano 6:54349–68
    [Google Scholar]
  42. 42. 
    Adamcakova-Dodd A, Stebounova LV, Kim JS, Vorrink SU, Ault AP et al. 2014. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models. Part. Fibre Toxicol. 11:15
    [Google Scholar]
  43. 43. 
    Maher BA, Ahmed IAM, Karloukovski V, MacLaren DA, Foulds PG et al. 2016. Magnetite pollution nanoparticles in the human brain. PNAS 113:3910797–801
    [Google Scholar]
  44. 44. 
    Lin Y, Hu C, Chen A, Feng X, Liang H et al. 2020. Neurotoxicity of nanoparticles entering the brain via sensory nerve-to-brain pathways: injuries and mechanisms. Arch. Toxicol. 94:5147995
    [Google Scholar]
  45. 45. 
    Choi HS, Ashitate Y, Lee JH, Kim SH, Matsui A et al. 2010. Rapid translocation of nanoparticles from the lung airspaces to the body. Nat. Biotechnol. 28:121300–3
    [Google Scholar]
  46. 46. 
    Raftis JB, Miller MR. 2019. Nanoparticle translocation and multi-organ toxicity: a particularly small problem. Nano Today 26:8–12
    [Google Scholar]
  47. 47. 
    Moghimi SM, Simberg D. 2017. Complement activation turnover on surfaces of nanoparticles. Nano Today 15:8–10
    [Google Scholar]
  48. 48. 
    Szebeni J. 2014. Complement activation-related pseudoallergy: a stress reaction in blood triggered by nanomedicines and biologicals. Mol. Immunol. 61:2163–73
    [Google Scholar]
  49. 49. 
    Abu Lila AS, Kiwada H, Ishida T 2013. The accelerated blood clearance (ABC) phenomenon: clinical challenge and approaches to manage. J. Control. Release 172:138–47
    [Google Scholar]
  50. 50. 
    Dominguez-Medina S, Kisley L, Tauzin LJ, Hoggard A, Shuang B et al. 2016. Adsorption and unfolding of a single protein triggers nanoparticle aggregation. ACS Nano 10:22103–12
    [Google Scholar]
  51. 51. 
    Deng ZJ, Liang M, Monteiro M, Toth I, Minchin RF 2011. Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation. Nat. Nanotechnol. 6:139–44
    [Google Scholar]
  52. 52. 
    Saptarshi SR, Duschl A, Lopata AL 2013. Interaction of nanoparticles with proteins: relation to bio-reactivity of the nanoparticle. J. Nanobiotechnol. 11:126
    [Google Scholar]
  53. 53. 
    Neagu M, Piperigkou Z, Karamanou K, Engin AB, Docea AO et al. 2017. Protein bio-corona: critical issue in immune nanotoxicology. Arch. Toxicol. 91:31031–48
    [Google Scholar]
  54. 54. 
    Nel A, Xia T, Mädler L, Li N 2006. Toxic potential of materials at the nanolevel. Science 311:5761622–27
    [Google Scholar]
  55. 55. 
    Cedervall T, Lynch I, Lindman S, Berggård T, Thulin E et al. 2007. Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. PNAS 104:72050–55
    [Google Scholar]
  56. 56. 
    Linse S, Cabaleiro-Lago C, Xue W-F, Lynch I, Lindman S et al. 2007. Nucleation of protein fibrillation by nanoparticles. PNAS 104:218691–96
    [Google Scholar]
  57. 57. 
    Akhavan O, Ghaderi E. 2010. Toxicity of graphene and graphene oxide nanowalls against bacteria. ACS Nano 4:105731–36
    [Google Scholar]
  58. 58. 
    Chen KL, Bothun GD. 2014. Nanoparticles meet cell membranes: probing nonspecific interactions using model membranes. Environ. Sci. Technol. 48:2873–80
    [Google Scholar]
  59. 59. 
    Leifert A, Pan Y, Kinkeldey A, Schiefer F, Setzler J et al. 2013. Differential hERG ion channel activity of ultrasmall gold nanoparticles. PNAS 110:208004–9
    [Google Scholar]
  60. 60. 
    Fu PP, Xia Q, Hwang H-M, Ray PC, Yu H 2014. Mechanisms of nanotoxicity: generation of reactive oxygen species. J. Food Drug Anal. 22:164–75
    [Google Scholar]
  61. 61. 
    Abdal Dayem A, Hossain MK, Lee SB, Kim K, Saha SK et al. 2017. The role of reactive oxygen species (ROS) in the biological activities of metallic nanoparticles. Int. J. Mol. Sci. 18:1120
    [Google Scholar]
  62. 62. 
    Xia T, Kovochich M, Brant J, Hotze M, Sempf J et al. 2006. Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Lett 6:81794–807
    [Google Scholar]
  63. 63. 
    Zorov DB, Juhaszova M, Sollott SJ 2014. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol. Rev. 94:3909–50
    [Google Scholar]
  64. 64. 
    Pelaz B, Alexiou C, Alvarez-Puebla RA, Alves F, Andrews AM et al. 2017. Diverse applications of nanomedicine. ACS Nano 11:32313–81
    [Google Scholar]
  65. 65. 
    McShan D, Ray PC, Yu H 2014. Molecular toxicity mechanism of nanosilver. J. Food Drug Anal. 22:1116–27
    [Google Scholar]
  66. 66. 
    Tsoi KM, Dai Q, Alman BA, Chan WCW 2013. Are quantum dots toxic? Exploring the discrepancy between cell culture and animal studies. Acc. Chem. Res. 46:3662–71
    [Google Scholar]
  67. 67. 
    Chen N, He Y, Su Y, Li X, Huang Q et al. 2012. The cytotoxicity of cadmium-based quantum dots. Biomaterials 33:51238–44
    [Google Scholar]
  68. 68. 
    Derfus AM, Chan WCW, Bhatia SN 2004. Probing the cytotoxicity of semiconductor quantum dots. Nano Lett 4:111–18
    [Google Scholar]
  69. 69. 
    Hauck TS, Anderson RE, Fischer HC, Newbigging S, Chan WCW 2010. In vivo quantum-dot toxicity assessment. Small 6:1138–44
    [Google Scholar]
  70. 70. 
    Nishanth RP, Jyotsna RG, Schlager JJ, Hussain SM, Reddanna P 2011. Inflammatory responses of RAW 264.7 macrophages upon exposure to nanoparticles: role of ROS-NFκB signaling pathway. Nanotoxicology 5:4502–16
    [Google Scholar]
  71. 71. 
    Son Y, Cheong Y-K, Kim N-H, Chung H-T, Kang DG, Pae H-O 2011. Mitogen-activated protein kinases and reactive oxygen species: How can ROS activate MAPK pathways. ? J. Signal Transduct. 2011:792639
    [Google Scholar]
  72. 72. 
    Walter PL, Kampkötter A, Eckers A, Barthel A, Schmoll D et al. 2006. Modulation of FoxO signaling in human hepatoma cells by exposure to copper or zinc ions. Arch. Biochem. Biophys. 454:2107–13
    [Google Scholar]
  73. 73. 
    Frame MC. 2002. Src in cancer: deregulation and consequences for cell behaviour. Biochim. Biophys. Acta 1602:2114–30
    [Google Scholar]
  74. 74. 
    Nyga A, Hart A, Tetley TD 2015. Importance of the HIF pathway in cobalt nanoparticle-induced cytotoxicity and inflammation in human macrophages. Nanotoxicology 9:7905–17
    [Google Scholar]
  75. 75. 
    Weidemann A, Johnson RS. 2008. Biology of HIF-1α. Cell Death Differ 15:4621–27
    [Google Scholar]
  76. 76. 
    Angelé-Martínez C, Nguyen KVT, Ameer FS, Anker JN, Brumaghim JL 2017. Reactive oxygen species generation by copper(II) oxide nanoparticles determined by DNA damage assays and EPR spectroscopy. Nanotoxicology 11:2278–88
    [Google Scholar]
  77. 77. 
    Manke A, Wang L, Rojanasakul Y 2013. Mechanisms of nanoparticle-induced oxidative stress and toxicity. Biomed. Res. Int. 2013:942916
    [Google Scholar]
  78. 78. 
    Campisi L, Cummings RJ, Blander JM 2014. Death-defining immune responses after apoptosis. Am. J. Transplant. 14:71488–98
    [Google Scholar]
  79. 79. 
    Frank D, Vince JE. 2019. Pyroptosis versus necroptosis: similarities, differences, and crosstalk. Cell Death Differ 26:199–114
    [Google Scholar]
  80. 80. 
    Wang Q, Wang Y, Ding J, Wang C, Zhou X et al. 2020. A bioorthogonal system reveals antitumour immune function of pyroptosis. Nature 579:7799421–26
    [Google Scholar]
  81. 81. 
    Bergström K, Holmberg K, Safranj A, Hoffman AS, Edgell MJ et al. 1992. Reduction of fibrinogen adsorption on PEG-coated polystyrene surfaces. J. Biomed. Mater. Res. 26:6779–90
    [Google Scholar]
  82. 82. 
    Banerjee I, Pangule RC, Kane RS 2011. Antifouling coatings: recent developments in the design of surfaces that prevent fouling by proteins, bacteria, and marine organisms. Adv. Mater. 23:6690–718
    [Google Scholar]
  83. 83. 
    Chanan-Khan A, Szebeni J, Savay S, Liebes L, Rafique NM et al. 2003. Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil): possible role in hypersensitivity reactions. Ann. Oncol. 14:91430–37
    [Google Scholar]
  84. 84. 
    Ingen-Housz-Oro S, Pham-Ledard A, Brice P, Lebrun-Vignes B, Zehou O et al. 2017. Immediate hypersensitivity reaction to pegylated liposomal doxorubicin: management and outcome in four patients. Eur. J. Dermatol. 27:3271–74
    [Google Scholar]
  85. 85. 
    Szebeni J, Simberg D, González-Fernández Á, Barenholz Y, Dobrovolskaia MA 2018. Roadmap and strategy for overcoming infusion reactions to nanomedicines. Nat. Nanotechnol. 13:121100–8
    [Google Scholar]
  86. 86. 
    Ishida T, Wang X, Shimizu T, Nawata K, Kiwada H 2007. PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner. J. Control. Release 122:3349–55
    [Google Scholar]
  87. 87. 
    Wang X, Ishida T, Kiwada H 2007. Anti-PEG IgM elicited by injection of liposomes is involved in the enhanced blood clearance of a subsequent dose of PEGylated liposomes. J. Control. Release 119:2236–44
    [Google Scholar]
  88. 88. 
    Shimizu T, Mima Y, Hashimoto Y, Ukawa M, Ando H et al. 2015. Anti-PEG IgM and complement system are required for the association of second doses of PEGylated liposomes with splenic marginal zone B cells. Immunobiology 220:101151–60
    [Google Scholar]
  89. 89. 
    Mohamed M, Abu Lila AS, Shimizu T, Alaaeldin E, Hussein A et al. 2019. PEGylated liposomes: immunological responses. Sci. Technol. Adv. Mater. 20:1710–24
    [Google Scholar]
  90. 90. 
    Kozma GT, Mészáros T, Vashegyi I, Fülöp T, Örfi E et al. 2019. Pseudo-anaphylaxis to polyethylene glycol (PEG)-coated liposomes: roles of anti-PEG IgM and complement activation in a porcine model of human infusion reactions. ACS Nano 13:89315–24
    [Google Scholar]
  91. 91. 
    Chen F, Wang G, Griffin JI, Brenneman B, Banda NK et al. 2017. Complement proteins bind to nanoparticle protein corona and undergo dynamic exchange in vivo. Nat. Nanotechnol. 12:4387–93
    [Google Scholar]
  92. 92. 
    Povsic TJ, Lawrence MG, Lincoff AM, Mehran R, Rusconi CP et al. 2016. Pre-existing anti-PEG antibodies are associated with severe immediate allergic reactions to pegnivacogin, a PEGylated aptamer. J. Allergy Clin. Immunol. 138:61712–15
    [Google Scholar]
  93. 93. 
    Ganson NJ, Povsic TJ, Sullenger BA, Alexander JH, Zelenkofske SL et al. 2016. Pre-existing anti-polyethylene glycol antibody linked to first-exposure allergic reactions to pegnivacogin, a PEGylated RNA aptamer. J. Allergy Clin. Immunol. 137:51610–13.e7
    [Google Scholar]
  94. 94. 
    Finkelman FD. 2007. Anaphylaxis: lessons from mouse models. J. Allergy Clin. Immunol. 120:3506–15
    [Google Scholar]
  95. 95. 
    Zhang P, Sun F, Liu S, Jiang S 2016. Anti-PEG antibodies in the clinic: current issues and beyond PEGylation. J. Control. Release 244:184–93
    [Google Scholar]
  96. 96. 
    Yang Q, Jacobs TM, McCallen JD, Moore DT, Huckaby JT et al. 2016. Analysis of pre-existing IgG and IgM antibodies against polyethylene glycol (PEG) in the general population. Anal. Chem. 88:2311804–12
    [Google Scholar]
  97. 97. 
    DeAngelis PL. 2015. Heparosan, a promising ‘naturally good’ polymeric conjugating vehicle for delivery of injectable therapeutics. Expert Opin. Drug Deliv. 12:3349–52
    [Google Scholar]
  98. 98. 
    Chen E, Chen B-M, Su Y-C, Chang Y-C, Cheng T-L et al. 2020. Premature drug release from polyethylene glycol (PEG)-coated liposomal doxorubicin via formation of the membrane attack complex. ACS Nano 14:7780822
    [Google Scholar]
  99. 99. 
    Yang Q, Lai SK. 2015. Anti-PEG immunity: emergence, characteristics, and unaddressed questions. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 7:5655–77
    [Google Scholar]
  100. 100. 
    Afantitis A, Melagraki G, Isigonis P, Tsoumanis A, Varsou DD et al. 2020. NanoSolveIT Project: driving nanoinformatics research to develop innovative and integrated tools for in silico nanosafety assessment. Comput. Struct. Biotechnol. J. 18:583–602
    [Google Scholar]
  101. 101. 
    Furxhi I, Murphy F, Mullins M, Poland CA 2019. Machine learning prediction of nanoparticle in vitro toxicity: a comparative study of classifiers and ensemble-classifiers using the Copeland Index. Toxicol. Lett. 312:157–66
    [Google Scholar]
  102. 102. 
    Oh E, Liu R, Nel A, Gemill KB, Bilal M et al. 2016. Meta-analysis of cellular toxicity for cadmium-containing quantum dots. Nat. Nanotechnol. 11:5479–86
    [Google Scholar]
  103. 103. 
    Kolanjiyil AV, Kleinstreuer C, Kleinstreuer NC, Pham W, Sadikot RT 2019. Mice-to-men comparison of inhaled drug-aerosol deposition and clearance. Respir. Physiol. Neurobiol. 260:82–94
    [Google Scholar]
  104. 104. 
    Ha MK, Trinh TX, Choi JS, Maulina D, Byun HG, Yoon TH 2018. Toxicity classification of oxide nanomaterials: effects of data gap filling and PChem score-based screening approaches. Sci. Rep. 8:13141
    [Google Scholar]
  105. 105. 
    Leong HS, Butler KS, Brinker CJ, Azzawi M, Conlan S et al. 2019. On the issue of transparency and reproducibility in nanomedicine. Nat. Nanotechnol. 14:7629–35
    [Google Scholar]
  106. 106. 
    Eftekhari A, Dizaj SM, Chodari L, Sunar S, Hasanzadeh A et al. 2018. The promising future of nano-antioxidant therapy against environmental pollutants induced-toxicities. Biomed. Pharmacother. 103:1018–27
    [Google Scholar]
  107. 107. 
    Buchman JT, Hudson-Smith NV, Landy KM, Haynes CL 2019. Understanding nanoparticle toxicity mechanisms to inform redesign strategies to reduce environmental impact. Acc. Chem. Res. 52:61632–42
    [Google Scholar]
  108. 108. 
    Wilhelm S, Kaiser M, Würth C, Heiland J, Carrillo-Carrion C et al. 2015. Water dispersible upconverting nanoparticles: effects of surface modification on their luminescence and colloidal stability. Nanoscale 7:41403–10
    [Google Scholar]
  109. 109. 
    Wilhelm S. 2017. Perspectives for upconverting nanoparticles. ACS Nano 11:1110644–53
    [Google Scholar]
  110. 110. 
    Wilhelm S, Hirsch T, Patterson WM, Scheucher E, Mayr T, Wolfbeis OS 2013. Multicolor upconversion nanoparticles for protein conjugation. Theranostics 3:4239–48
    [Google Scholar]
  111. 111. 
    Rao L, Meng Q-F, Bu L-L, Cai B, Huang Q et al. 2017. Erythrocyte membrane-coated upconversion nanoparticles with minimal protein adsorption for enhanced tumor imaging. ACS Appl. Mater. Interfaces 9:32159–68
    [Google Scholar]
  112. 112. 
    Dolez PI, Bodila N, Lara J, Truchon G 2009. Personal protective equipment against nanoparticles. Int. J. Nanotechnol. 7:199–117
    [Google Scholar]
  113. 113. 
    Nat. Nanotechnol. Ed. Board. 2020. The risks of nanomaterial risk assessment. Nat. Nanotechnol 15:163
    [Google Scholar]
  114. 114. 
    Hansen SF, Lennquist A. 2020. Carbon nanotubes added to the SIN List as a nanomaterial of Very High Concern. Nat. Nanotechnol. 15:13–4
    [Google Scholar]
  115. 115. 
    Fadeel B, Kostarelos K. 2020. Grouping all carbon nanotubes into a single substance category is scientifically unjustified. Nat. Nanotechnol. 15:3164
    [Google Scholar]
  116. 116. 
    Heller DA, Jena PV, Pasquali M, Kostarelos K, Delogu LG et al. 2020. Banning carbon nanotubes would be scientifically unjustified and damaging to innovation. Nat. Nanotechnol. 15:164–66
    [Google Scholar]
  117. 117. 
    Shatkin JA. 2020. The future in nanosafety. Nano Lett 20:31479–80
    [Google Scholar]
  118. 118. 
    Fadeel B. 2019. The right stuff: on the future of nanotoxicology. Front. Toxicol. 1:1
    [Google Scholar]
  119. 119. 
    Faria M, Björnmalm M, Thurecht KJ, Kent SJ, Parton RG et al. 2018. Minimum information reporting in bio-nano experimental literature. Nat. Nanotechnol. 13:9777–85
    [Google Scholar]
  120. 120. 
    Schrand AM, Rahman MF, Hussain SM, Schlager JJ, Smith DA, Syed AF 2010. Metal-based nanoparticles and their toxicity assessment. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2:5544–68
    [Google Scholar]
  121. 121. 
    Nel A, Xia T, Meng H, Wang X, Lin S et al. 2013. Nanomaterial toxicity testing in the 21st century: use of a predictive toxicological approach and high-throughput screening. Acc. Chem. Res. 46:3607–21
    [Google Scholar]
  122. 122. 
    Watson C, Ge J, Cohen J, Pyrgiotakis G, Engelward BP, Demokritou P 2014. High-throughput screening platform for engineered nanoparticle-mediated genotoxicity using CometChip technology. ACS Nano 8:32118–33
    [Google Scholar]
  123. 123. 
    De Simone U, Roccio M, Gribaldo L, Spinillo A, Caloni F, Coccini T 2018. Human 3D cultures as models for evaluating magnetic nanoparticle CNS cytotoxicity after short- and repeated long-term exposure. Int. J. Mol. Sci. 19:71993
    [Google Scholar]
  124. 124. 
    Steger-Hartmann T, Raschke M. 2020. Translating in vitro to in vivo and animal to human. Curr. Opin. Toxicol. 23–24:6–10
    [Google Scholar]
  125. 125. 
    Zink D, Chuah JKC, Ying JY 2020. Assessing toxicity with human cell-based in vitro methods. Trends Mol. Med. 26:657082
    [Google Scholar]
  126. 126. 
    Sindhwani S, Syed AM, Wilhelm S, Glancy DR, Chen YY et al. 2016. Three-dimensional optical mapping of nanoparticle distribution in intact tissues. ACS Nano 10:55468–78
    [Google Scholar]
  127. 127. 
    Sindhwani S, Syed AM, Wilhelm S, Chan WCW 2017. Exploring passive clearing for 3D optical imaging of nanoparticles in intact tissues. Bioconjug. Chem. 28:1253–59
    [Google Scholar]
  128. 128. 
    Syed AM, Sindhwani S, Wilhelm S, Kingston BR, Lee DSW et al. 2017. Three-dimensional imaging of transparent tissues via metal nanoparticle labeling. J. Am. Chem. Soc. 139:299961–71
    [Google Scholar]
  129. 129. 
    Syed AM, MacMillan P, Ngai J, Wilhelm S, Sindhwani S et al. 2020. Liposome imaging in optically cleared tissues. Nano Lett 20:21362–69
    [Google Scholar]
  130. 130. 
    Merrifield RC, Stephan C, Lead JR 2018. Quantification of Au nanoparticle biouptake and distribution to freshwater algae using single cell–ICP-MS. Environ. Sci. Technol. 52:42271–77
    [Google Scholar]
  131. 131. 
    Wilhelm S, Bensen RC, Kothapalli NR, Burgett AWG, Merrifield R, Stephan C 2018. Quantification of gold nanoparticle uptake into cancer cells using single cell ICP-MS Appl. Note, PerkinElmer Waltham, MA:
  132. 132. 
    Fang RH, Kroll AV, Gao W, Zhang L 2018. Cell membrane coating nanotechnology. Adv. Mater. 30:23e1706759
    [Google Scholar]
  133. 133. 
    Golabchi A, Wu B, Cao B, Bettinger CJ, Cui XT 2019. Zwitterionic polymer/polydopamine coating reduce acute inflammatory tissue responses to neural implants. Biomaterials 225:119519
    [Google Scholar]
  134. 134. 
    Kim K, Choi H, Choi ES, Park M-H, Ryu J-H 2019. Hyaluronic acid-coated nanomedicine for targeted cancer therapy. Pharmaceutics 11:7301
    [Google Scholar]
  135. 135. 
    Zhang T, Zhou S, Hu L, Peng B, Liu Y et al. 2016. Polysialic acid-modifying liposomes for efficient delivery of epirubicin, in-vitro characterization and in-vivo evaluation. Int. J. Pharm. 515:1449–59
    [Google Scholar]
  136. 136. 
    Lane RS, Haller FM, Chavaroche AAE, Almond A, DeAngelis PL 2017. Heparosan-coated liposomes for drug delivery. Glycobiology 27:111062–74
    [Google Scholar]
  137. 137. 
    Lazarovits J, Chen YY, Song F, Ngo W, Tavares AJ et al. 2019. Synthesis of patient-specific nanomaterials. Nano Lett 19:1116–23
    [Google Scholar]
  138. 138. 
    Akaighe N, Maccuspie RI, Navarro DA, Aga DS, Banerjee S et al. 2011. Humic acid-induced silver nanoparticle formation under environmentally relevant conditions. Environ. Sci. Technol. 45:93895–901
    [Google Scholar]
  139. 139. 
    Glover RD, Miller JM, Hutchison JE 2011. Generation of metal nanoparticles from silver and copper objects: nanoparticle dynamics on surfaces and potential sources of nanoparticles in the environment. ACS Nano 5:118950–57
    [Google Scholar]
  140. 140. 
    Zheng Y, Lee PW, Wang C, Thomas LD, Stewart PL et al. 2019. Freeze-drying to produce efficacious CPMV virus-like particles. Nano Lett 19:32099–105
    [Google Scholar]
  141. 141. 
    Guo B, Zebda R, Drake SJ, Sayes CM 2009. Synergistic effect of co-exposure to carbon black and Fe2O3 nanoparticles on oxidative stress in cultured lung epithelial cells. Part. Fibre Toxicol. 6:4
    [Google Scholar]
  142. 142. 
    Andriyanov AV, Koren E, Barenholz Y, Goldberg SN 2014. Therapeutic efficacy of combining pegylated liposomal doxorubicin and radiofrequency (RF) ablation: comparison between slow-drug-releasing, non-thermosensitive and fast-drug-releasing, thermosensitive nano-liposomes. PLOS ONE 9:5e92555
    [Google Scholar]
  143. 143. 
    Pankhurst Q, Hautot D, Khan N, Dobson J 2008. Increased levels of magnetic iron compounds in Alzheimer's disease. J. Alzheimer's Dis. 13:149–52
    [Google Scholar]
  144. 144. 
    Khatri M, Bello D, Gaines P, Martin J, Pal AK et al. 2013. Nanoparticles from photocopiers induce oxidative stress and upper respiratory tract inflammation in healthy volunteers. Nanotoxicology 7:51014–27
    [Google Scholar]
  145. 145. 
    Aktepe N, Kocyigit A, Yukselten Y, Taskin A, Keskin C, Celik H 2015. Increased DNA damage and oxidative stress among silver jewelry workers. Biol. Trace Elem. Res. 164:2185–91
    [Google Scholar]
  146. 146. 
    Munger MA, Radwanski P, Hadlock GC, Stoddard G, Shaaban A et al. 2014. In vivo human time-exposure study of orally dosed commercial silver nanoparticles. Nanomedicine 10:11–9
    [Google Scholar]
  147. 147. 
    Hussain SM, Hess KL, Gearhart JM, Geiss KT, Schlager JJ 2005. In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol. In Vitro 19:7975–83
    [Google Scholar]
  148. 148. 
    Lee J, Lilly GD, Doty RC, Podsiadlo P, Kotov NA 2009. In vitro toxicity testing of nanoparticles in 3D cell culture. Small 5:101213–21
    [Google Scholar]
  149. 149. 
    Kumar G, Degheidy H, Casey BJ, Goering PL 2015. Flow cytometry evaluation of in vitro cellular necrosis and apoptosis induced by silver nanoparticles. Food Chem. Toxicol. 85:45–51
    [Google Scholar]
  150. 150. 
    Lewinski N, Colvin V, Drezek R 2008. Cytotoxicity of nanoparticles. Small 4:126–49
    [Google Scholar]
  151. 151. 
    Trouiller B, Reliene R, Westbrook A, Solaimani P, Schiestl RH 2009. Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer Res 69:228784–89
    [Google Scholar]
  152. 152. 
    Evans BC, Nelson CE, Yu SS, Beavers KR, Kim AJ et al. 2013. Ex vivo red blood cell hemolysis assay for the evaluation of pH-responsive endosomolytic agents for cytosolic delivery of biomacromolecular drugs. J. Vis. Exp. 73:50166
    [Google Scholar]
  153. 153. 
    Elsabahy M, Wooley KL. 2013. Cytokines as biomarkers of nanoparticle immunotoxicity. Chem. Soc. Rev. 42:125552–76
    [Google Scholar]
  154. 154. 
    Kirchner C, Liedl T, Kudera S, Pellegrino T, Muñoz Javier A et al. 2005. Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. Nano Lett 5:2331–38
    [Google Scholar]
  155. 155. 
    Wörle-Knirsch JM, Pulskamp K, Krug HF 2006. Oops they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Lett 6:61261–68
    [Google Scholar]
  156. 156. 
    Lynch I, Dawson KA, Linse S 2006. Detecting cryptic epitopes created by nanoparticles. Sci. STKE 2006:327pe14
    [Google Scholar]
  157. 157. 
    Zhao J, Riediker M. 2014. Detecting the oxidative reactivity of nanoparticles: a new protocol for reducing artifacts. J. Nanopart. Res. 16:72493
    [Google Scholar]
  158. 158. 
    Balke J, Volz P, Neumann F, Brodwolf R, Wolf A et al. 2018. Visualizing oxidative cellular stress induced by nanoparticles in the subcytotoxic range using fluorescence lifetime imaging. Small 14:23e1800310
    [Google Scholar]
  159. 159. 
    Rajkumar KS, Kanipandian N, Thirumurugan R 2016. Toxicity assessment on haemotology, biochemical and histopathological alterations of silver nanoparticles-exposed freshwater fish Labeo rohita. Appl. Nanosci 6:119–29
    [Google Scholar]
  160. 160. 
    Yang Y, Qin Z, Zeng W, Yang T, Cao Y et al. 2017. Toxicity assessment of nanoparticles in various systems and organs. Nanotechnol. Rev. 6:3279–89
    [Google Scholar]
  161. 161. 
    Hoshyar N, Gray S, Han H, Bao G 2016. The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction. Nanomedicine 11:6673–92
    [Google Scholar]
  162. 162. 
    Bobo D, Robinson KJ, Islam J, Thurecht KJ, Corrie SR 2016. Nanoparticle-based medicines: a review of FDA-approved materials and clinical trials to date. Pharm. Res. 33:102373–87
    [Google Scholar]
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