Increased Toxicity Risk from Nanoparticulate System in Food and Drug Applications
DOI:
https://doi.org/10.22437/ifstj.v8i2.40494Keywords:
nanoparticles, toxicity, physicochemical properties, oxidative stress, inflammationAbstract
Abstract— Nanotechnology involves manipulating matter at the atomic and molecular levels, leading to the creation of new materials for food and drug application with properties that are not always easily anticipated based on existing knowledge. Among the nearly infinite variety of these substances, some are toxic to biological systems, others are generally harmless, and yet others confer health advantages. The biocompatibility and distribution of these materials must be assessed prior to their use in biological and environmental. Consequently, it is essential to comprehend the toxicity of nanomaterials. Mechanisms of cellular uptake and nanoparticles dispersion in biological settings depend on their physicochemical properties. The pathways in which exposure to nanoparticles is harmful to health are through oxidative stress and inflammation. Recent research have indicated that nanoparticles may cause major health impacts when ingested, inhaled, or applied to the skin without precaution. The main sources of toxicity in nanomaterials include their size, shape, concentration, aspect ratio, crystallinity, surface charge, dissolution, and agglomeration. This review article aims to comprehensively summarize the toxicity aspects of nanoparticles for food and drug application, including physiochemical properties, mechanisms of nanoparticle toxicity, and the health risks, so as to provide an overview for future researchers to develop nanoparticulate in a safer way.
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[1] M. Aliofkhazrei, Handbook of Nanoparticles. Cham: Springer International Publishing, 2016. doi: 10.1007/978-3-319-15338-4.
[2] M. C. Garnett and P. Kallinteri, “Nanomedicines and nanotoxicology: some physiological principles,” Occup. Med. (Chic. Ill)., vol. 56, no. 5, pp. 307–311, Aug. 2006, doi: 10.1093/occmed/kql052.
[3] M. Milić et al., “Cellular uptake and toxicity effects of silver nanoparticles in mammalian kidney cells,” J. Appl. Toxicol., vol. 35, no. 6, pp. 581–592, Jun. 2015, doi: 10.1002/jat.3081.
[4] A. M. El-Khawaga, A. Zidan, and A. I. A. A. El-Mageed, “Preparation methods of different nanomaterials for various potential applications: A review,” J. Mol. Struct., vol. 1281, p. 135148, Jun. 2023, doi: 10.1016/j.molstruc.2023.135148.
[5] F. ud Din et al., “Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors,” Int. J. Nanomedicine, vol. Volume 12, pp. 7291–7309, Oct. 2017, doi: 10.2147/IJN.S146315.
[6] G. Oberdörster, E. Oberdörster, and J. Oberdörster, “Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles,” Environ. Health Perspect., vol. 113, no. 7, pp. 823–839, Jul. 2005, doi: 10.1289/ehp.7339.
[7] B. Yameen, W. Il Choi, C. Vilos, A. Swami, J. Shi, and O. C. Farokhzad, “Insight into nanoparticle cellular uptake and intracellular targeting,” J. Control. Release, vol. 190, pp. 485–499, Sep. 2014, doi: 10.1016/j.jconrel.2014.06.038.
[8] A. Sukhanova, S. Bozrova, P. Sokolov, M. Berestovoy, A. Karaulov, and I. Nabiev, “Dependence of Nanoparticle Toxicity on Their Physical and Chemical Properties,” Nanoscale Res. Lett., vol. 13, no. 1, p. 44, Dec. 2018, doi: 10.1186/s11671-018-2457-x.
[9] K. Donaldson et al., “Carbon Nanotubes: A Review of Their Properties in Relation to Pulmonary Toxicology and Workplace Safety,” Toxicol. Sci., vol. 92, no. 1, pp. 5–22, Jul. 2006, doi: 10.1093/toxsci/kfj130.
[10] J. Jeevanandam, Y. S. Chan, and M. K. Danquah, “Biosynthesis of Metal and Metal Oxide Nanoparticles,” ChemBioEng Rev., vol. 3, no. 2, pp. 55–67, Apr. 2016, doi: 10.1002/cben.201500018.
[11] S. Naz, A. Gul, and M. Zia, “Toxicity of copper oxide nanoparticles: a review study,” IET Nanobiotechnology, vol. 14, no. 1, pp. 1–13, Feb. 2020, doi: 10.1049/iet-nbt.2019.0176.
[12] S. Roy, R. Sadhukhan, U. Ghosh, and T. K. Das, “Interaction studies between biosynthesized silver nanoparticle with calf thymus DNA and cytotoxicity of silver nanoparticles,” Spectrochim. Acta Part A Mol. Biomol. Spectrosc., vol. 141, pp. 176–184, Apr. 2015, doi: 10.1016/j.saa.2015.01.041.
[13] D. B. Warheit, “Comparative Pulmonary Toxicity Assessment of Single-wall Carbon Nanotubes in Rats,” Toxicol. Sci., vol. 77, no. 1, pp. 117–125, Dec. 2003, doi: 10.1093/toxsci/kfg228.
[14] I. Beck-Speier et al., “Oxidative stress and lipid mediators induced in alveolar macrophages by ultrafine particles,” Free Radic. Biol. Med., vol. 38, no. 8, pp. 1080–1092, Apr. 2005, doi: 10.1016/j.freeradbiomed.2005.01.004.
[15] P. J. A. Borm and W. Kreyling, “Toxicological Hazards of Inhaled Nanoparticles—Potential Implications for Drug Delivery,” J. Nanosci. Nanotechnol., vol. 4, no. 5, pp. 521–531, May 2004, doi: 10.1166/jnn.2004.081.
[16] M. Ajdary, F. Keyhanfar, M. A. Moosavi, R. Shabani, M. Mehdizadeh, and R. S. Varma, “Potential toxicity of nanoparticles on the reproductive system animal models: A review,” J. Reprod. Immunol., vol. 148, p. 103384, Nov. 2021, doi: 10.1016/j.jri.2021.103384.
[17] M. Ema, K. S. Hougaard, A. Kishimoto, and K. Honda, “Reproductive and developmental toxicity of carbon-based nanomaterials: A literature review,” Nanotoxicology, vol. 10, no. 4, pp. 391–412, Apr. 2016, doi: 10.3109/17435390.2015.1073811.
[18] A. M. Derfus, W. C. W. Chan, and S. N. Bhatia, “Probing the Cytotoxicity of Semiconductor Quantum Dots,” Nano Lett., vol. 4, no. 1, pp. 11–18, Jan. 2004, doi: 10.1021/nl0347334.
[19] C.-C. Chou et al., “Single-Walled Carbon Nanotubes Can Induce Pulmonary Injury in Mouse Model,” Nano Lett., vol. 8, no. 2, pp. 437–445, Feb. 2008, doi: 10.1021/nl0723634.
[20] P. Lin et al., “Computational and Ultrastructural Toxicology of a Nanoparticle, Quantum Dot 705, in Mice,” Environ. Sci. Technol., vol. 42, no. 16, pp. 6264–6270, Aug. 2008, doi: 10.1021/es800254a.
[21] M. L. Schipper et al., “A pilot toxicology study of single-walled carbon nanotubes in a small sample of mice,” Nat. Nanotechnol., vol. 3, no. 4, pp. 216–221, Apr. 2008, doi: 10.1038/nnano.2008.68.
[22] M. E. Vance et al., “Nanotechnology in the real world: Redeveloping the nanomaterial consumer products inventory,” Beilstein J. Nanotechnol., vol. 6, pp. 1769–1780, Aug. 2015, doi: 10.3762/bjnano.6.181.
[23] M. Bartneck et al., “Peptide-Functionalized Gold Nanorods Increase Liver Injury in Hepatitis,” ACS Nano, vol. 6, no. 10, pp. 8767–8777, Oct. 2012, doi: 10.1021/nn302502u.
[24] J. Wu, C. Wang, J. Sun, and Y. Xue, “Neurotoxicity of Silica Nanoparticles: Brain Localization and Dopaminergic Neurons Damage Pathways,” ACS Nano, vol. 5, no. 6, pp. 4476–4489, Jun. 2011, doi: 10.1021/nn103530b.
[25] X. Liu, T. Bing, and D. Shangguan, “Microbead-Based Platform for Multiplex Detection of DNA and Protein,” ACS Appl. Mater. Interfaces, vol. 9, no. 11, pp. 9462–9469, Mar. 2017, doi: 10.1021/acsami.7b00418.
[26] M. Muhaimin, A. Y. Chaerunisaa, and R. Bodmeier, “Preparation and evaluation of various formulation effects of the second emulsion on the shape and release profile of propranolol HCl from ethyl cellulose microparticle blends,” Polym. Int., vol. 72, no. 3, pp. 383–391, Mar. 2023, doi: 10.1002/pi.6480.
[27] C. Buzea, I. I. Pacheco, and K. Robbie, “Nanomaterials and nanoparticles: Sources and toxicity,” Biointerphases, vol. 2, no. 4, pp. MR17–MR71, Dec. 2007, doi: 10.1116/1.2815690.
[28] S. Albukhaty, H. Naderi-Manesh, and T. Tiraihi, “In vitro labeling of neural stem cells with poly-L-lysine coated super paramagnetic nanoparticles for green fluorescent protein transfection.,” Iran. Biomed. J., vol. 17, no. 2, pp. 71–76, Apr. 2013, doi: 10.6091/ibj.1114.2013.
[29] Naqvi et al., “Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress,” Int. J. Nanomedicine, p. 983, Nov. 2010, doi: 10.2147/IJN.S13244.
[30] G. Liu, J. Gao, H. Ai, and X. Chen, “Applications and Potential Toxicity of Magnetic Iron Oxide Nanoparticles,” Small, vol. 9, no. 9–10, pp. 1533–1545, May 2013, doi: 10.1002/smll.201201531.
[31] M.-T. Zhu et al., “Comparative study of pulmonary responses to nano- and submicron-sized ferric oxide in rats,” Toxicology, vol. 247, no. 2–3, pp. 102–111, May 2008, doi: 10.1016/j.tox.2008.02.011.
[32] E. Pawelczyk, A. S. Arbab, A. Chaudhry, A. Balakumaran, P. G. Robey, and J. A. Frank, “In Vitro Model of Bromodeoxyuridine or Iron Oxide Nanoparticle Uptake by Activated Macrophages from Labeled Stem Cells: Implications for Cellular Therapy,” Stem Cells, vol. 26, no. 5, pp. 1366–1375, May 2008, doi: 10.1634/stemcells.2007-0707.
[33] H. A. JENG and J. SWANSON, “Toxicity of Metal Oxide Nanoparticles in Mammalian Cells,” J. Environ. Sci. Heal. Part A, vol. 41, no. 12, pp. 2699–2711, Dec. 2006, doi: 10.1080/10934520600966177.
[34] Y. Ge, Y. Zhang, S. He, F. Nie, G. Teng, and N. Gu, “Fluorescence Modified Chitosan-Coated Magnetic Nanoparticles for High-Efficient Cellular Imaging,” Nanoscale Res. Lett., vol. 4, no. 4, p. 287, Apr. 2009, doi: 10.1007/s11671-008-9239-9.
[35] G. J.-R. Delcroix et al., “Mesenchymal and neural stem cells labeled with HEDP-coated SPIO nanoparticles: In vitro characterization and migration potential in rat brain,” Brain Res., vol. 1255, pp. 18–31, Feb. 2009, doi: 10.1016/j.brainres.2008.12.013.
[36] L. Chen, R. A. Yokel, B. Hennig, and M. Toborek, “Manufactured Aluminum Oxide Nanoparticles Decrease Expression of Tight Junction Proteins in Brain Vasculature,” J. Neuroimmune Pharmacol., vol. 3, no. 4, pp. 286–295, Dec. 2008, doi: 10.1007/s11481-008-9131-5.
[37] E. Radziun et al., “Assessment of the cytotoxicity of aluminium oxide nanoparticles on selected mammalian cells,” Toxicol. Vitr., vol. 25, no. 8, pp. 1694–1700, Dec. 2011, doi: 10.1016/j.tiv.2011.07.010.
[38] A. A. Alshatwi, P. Vaiyapuri Subbarayan, E. Ramesh, A. A. Al‐Hazzani, M. A. Alsaif, and A. A. Alwarthan, “Al 2 O 3 Nanoparticles Induce Mitochondria‐Mediated Cell Death and Upregulate the Expression of Signaling Genes in Human Mesenchymal Stem Cells,” J. Biochem. Mol. Toxicol., vol. 26, no. 11, pp. 469–476, Nov. 2012, doi: 10.1002/jbt.21448.
[39] A. Balasubramanyam, N. Sailaja, M. Mahboob, M. F. Rahman, S. M. Hussain, and P. Grover, “In vivo genotoxicity assessment of aluminium oxide nanomaterials in rat peripheral blood cells using the comet assay and micronucleus test,” Mutagenesis, vol. 24, no. 3, pp. 245–251, May 2009, doi: 10.1093/mutage/gep003.
[40] R. J. Kim YJ, Choi HS, Song MK, Youk DY, Kim JH, “Genotoxicity of Aluminum Oxide (Al1O3) Nanoparticle in Mammalian Cell Lines.,” Mol. Cell. Toxicol., vol. 5, pp. 172–178, 2009.
[41] R. Liu et al., “Pulmonary toxicity induced by three forms of titanium dioxide nanoparticles via intra-tracheal instillation in rats,” Prog. Nat. Sci., vol. 19, no. 5, pp. 573–579, May 2009, doi: 10.1016/j.pnsc.2008.06.020.
[42] B. Trouiller, R. Reliene, A. Westbrook, P. Solaimani, and R. H. Schiestl, “Titanium Dioxide Nanoparticles Induce DNA Damage and Genetic Instability In vivo in Mice,” Cancer Res., vol. 69, no. 22, pp. 8784–8789, Nov. 2009, doi: 10.1158/0008-5472.CAN-09-2496.
[43] K. Bhattacharya, M. Davoren, J. Boertz, R. P. Schins, E. Hoffmann, and E. Dopp, “Titanium dioxide nanoparticles induce oxidative stress and DNA-adduct formation but not DNA-breakage in human lung cells,” Part. Fibre Toxicol., vol. 6, no. 1, p. 17, Dec. 2009, doi: 10.1186/1743-8977-6-17.
[44] H. Liu et al., “Erratum to: Biochemical Toxicity of Nano-anatase TiO2 Particles in Mice,” Biol. Trace Elem. Res., vol. 160, no. 1, pp. 152–152, Jul. 2014, doi: 10.1007/s12011-014-0011-y.
[45] R. Liu et al., “Small-Sized Titanium Dioxide Nanoparticles Mediate Immune Toxicity in Rat Pulmonary Alveolar Macrophages In Vivo,” J. Nanosci. Nanotechnol., vol. 10, no. 8, pp. 5161–5169, Aug. 2010, doi: 10.1166/jnn.2010.2420.
[46] N. Durán, M. Durán, M. B. de Jesus, A. B. Seabra, W. J. Fávaro, and G. Nakazato, “Silver nanoparticles: A new view on mechanistic aspects on antimicrobial activity,” Nanomedicine Nanotechnology, Biol. Med., vol. 12, no. 3, pp. 789–799, Apr. 2016, doi: 10.1016/j.nano.2015.11.016.
[47] N. Durán, G. Nakazato, and A. B. Seabra, “Antimicrobial activity of biogenic silver nanoparticles, and silver chloride nanoparticles: an overview and comments,” Appl. Microbiol. Biotechnol., vol. 100, no. 15, pp. 6555–6570, Aug. 2016, doi: 10.1007/s00253-016-7657-7.
[48] K. Venugopal et al., “The impact of anticancer activity upon Beta vulgaris extract mediated biosynthesized silver nanoparticles (ag-NPs) against human breast (MCF-7), lung (A549) and pharynx (Hep-2) cancer cell lines,” J. Photochem. Photobiol. B Biol., vol. 173, pp. 99–107, Aug. 2017, doi: 10.1016/j.jphotobiol.2017.05.031.
[49] R. Foldbjerg, D. A. Dang, and H. Autrup, “Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549,” Arch. Toxicol., vol. 85, no. 7, pp. 743–750, Jul. 2011, doi: 10.1007/s00204-010-0545-5.
[50] D. A. M. Kheirallah, L. M. El-Samad, and A. M. Abdel-Moneim, “DNA damage and ovarian ultrastructural lesions induced by nickel oxide nano-particles in Blaps polycresta (Coleoptera: Tenebrionidae),” Sci. Total Environ., vol. 753, p. 141743, Jan. 2021, doi: 10.1016/j.scitotenv.2020.141743.
[51] P. Kovvuru, P. E. Mancilla, A. B. Shirode, T. M. Murray, T. J. Begley, and R. Reliene, “Oral ingestion of silver nanoparticles induces genomic instability and DNA damage in multiple tissues,” Nanotoxicology, vol. 9, no. 2, pp. 162–171, Feb. 2015, doi: 10.3109/17435390.2014.902520.
[52] E. E. Connor, J. Mwamuka, A. Gole, C. J. Murphy, and M. D. Wyatt, “Gold Nanoparticles Are Taken Up by Human Cells but Do Not Cause Acute Cytotoxicity,” Small, vol. 1, no. 3, pp. 325–327, Mar. 2005, doi: 10.1002/smll.200400093.
[53] C. M. Goodman, C. D. McCusker, T. Yilmaz, and V. M. Rotello, “Toxicity of Gold Nanoparticles Functionalized with Cationic and Anionic Side Chains,” Bioconjug. Chem., vol. 15, no. 4, pp. 897–900, Jul. 2004, doi: 10.1021/bc049951i.
[54] E. Boisselier and D. Astruc, “Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity,” Chem. Soc. Rev., vol. 38, no. 6, p. 1759, 2009, doi: 10.1039/b806051g.
[55] M. Muhaimin, A. Y. Chaerunisaa, And A. Hazrina, “Preparation And Evaluation of Propranolol Hcl and Carbamazepine Release Profiles From Poly(Є-Caprolactone) Microparticle Blends System,” Int. J. Appl. Pharm., pp. 117–122, Sep. 2023, doi: 10.22159/ijap.2023v15i5.48574.
[56] M. Senut, Y. Zhang, F. Liu, A. Sen, D. M. Ruden, and G. Mao, “Size‐Dependent Toxicity of Gold Nanoparticles on Human Embryonic Stem Cells and Their Neural Derivatives,” Small, vol. 12, no. 5, pp. 631–646, Feb. 2016, doi: 10.1002/smll.201502346.
[57] A. Huczko, “Synthesis of aligned carbon nanotubes,” Appl. Phys. A Mater. Sci. Process., vol. 74, no. 5, pp. 617–638, May 2002, doi: 10.1007/s003390100929.
[58] P. Kesharwani, R. Ghanghoria, and N. K. Jain, “Carbon nanotube exploration in cancer cell lines,” Drug Discov. Today, vol. 17, no. 17–18, pp. 1023–1030, Sep. 2012, doi: 10.1016/j.drudis.2012.05.003.
[59] B. Gorain et al., “Carbon nanotube scaffolds as emerging nanoplatform for myocardial tissue regeneration: A review of recent developments and therapeutic implications,” Biomed. Pharmacother., vol. 104, pp. 496–508, Aug. 2018, doi: 10.1016/j.biopha.2018.05.066.
[60] C. A. Poland et al., “Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study,” Nat. Nanotechnol., vol. 3, no. 7, pp. 423–428, Jul. 2008, doi: 10.1038/nnano.2008.111.
[61] S.-T. Yang et al., “Long-term accumulation and low toxicity of single-walled carbon nanotubes in intravenously exposed mice,” Toxicol. Lett., vol. 181, no. 3, pp. 182–189, Oct. 2008, doi: 10.1016/j.toxlet.2008.07.020.
[62] K. PULSKAMP, S. DIABATE, and H. KRUG, “Carbon nanotubes show no sign of acute toxicity but induce intracellular reactive oxygen species in dependence on contaminants,” Toxicol. Lett., vol. 168, no. 1, pp. 58–74, Jan. 2007, doi: 10.1016/j.toxlet.2006.11.001.
[63] B. Gholamine, I. Karimi, A. Salimi, P. Mazdarani, and L. A. Becker, “Neurobehavioral toxicity of carbon nanotubes in mice,” Toxicol. Ind. Health, vol. 33, no. 4, pp. 340–350, Apr. 2017, doi: 10.1177/0748233716644381.
[64] H. Chen et al., “Single-walled carbon nanotubes modulate pulmonary immune responses and increase pandemic influenza a virus titers in mice,” Virol. J., vol. 14, no. 1, p. 242, Dec. 2017, doi: 10.1186/s12985-017-0909-z.
[65] E.-J. Park et al., “Subchronic immunotoxicity and screening of reproductive toxicity and developmental immunotoxicity following single instillation of HIPCO-single-walled carbon nanotubes: purity-based comparison,” Nanotoxicology, vol. 10, no. 8, pp. 1188–1202, Sep. 2016, doi: 10.1080/17435390.2016.1202348.
[66] D. Khang, S. Lee, and S.-H. Kim, “High dispersity of carbon nanotubes diminishes immunotoxicity in spleen,” Int. J. Nanomedicine, p. 2697, Apr. 2015, doi: 10.2147/IJN.S80836.
[67] M. Bottini et al., “Multi-walled carbon nanotubes induce T lymphocyte apoptosis,” Toxicol. Lett., vol. 160, no. 2, pp. 121–126, Jan. 2006, doi: 10.1016/j.toxlet.2005.06.020.
[68] S. F. Larner, J. Wang, J. Goodman, M. B. O’Donoghue Altman, M. Xin, and K. K. W. Wang, “In Vitro Neurotoxicity Resulting from Exposure of Cultured Neural Cells to Several Types of Nanoparticles,” J. Cell Death, vol. 10, p. 117967071769452, Jan. 2017, doi: 10.1177/1179670717694523.
[69] M. J. Aragon et al., “Serum-borne bioactivity caused by pulmonary multiwalled carbon nanotubes induces neuroinflammation via blood–brain barrier impairment,” Proc. Natl. Acad. Sci., vol. 114, no. 10, Mar. 2017, doi: 10.1073/pnas.1616070114.
[70] G. Bozzuto and A. Molinari, “Liposomes as nanomedical devices,” Int. J. Nanomedicine, p. 975, Feb. 2015, doi: 10.2147/IJN.S68861.
[71] S. M. Moghimi and J. Szebeni, “Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties,” Prog. Lipid Res., vol. 42, no. 6, pp. 463–478, Nov. 2003, doi: 10.1016/S0163-7827(03)00033-X.
[72] R. Fanciullino and J. Ciccolini, “Liposome-Encapsulated Anticancer Drugs: Still Waiting for the Magic Bullet?,” Curr. Med. Chem., vol. 16, no. 33, pp. 4361–4373, Nov. 2009, doi: 10.2174/092986709789712916.
[73] M. Alavi, N. Karimi, and M. Safaei, “Application of Various Types of Liposomes in Drug Delivery Systems,” Adv. Pharm. Bull., vol. 7, no. 1, pp. 3–9, Apr. 2017, doi: 10.15171/apb.2017.002.
[74] H. Daraee, A. Etemadi, M. Kouhi, S. Alimirzalu, and A. Akbarzadeh, “Application of liposomes in medicine and drug delivery,” Artif. Cells, Nanomedicine, Biotechnol., vol. 44, no. 1, pp. 381–391, Jan. 2016, doi: 10.3109/21691401.2014.953633.
[75] T. Nii and F. Ishii, “Encapsulation efficiency of water-soluble and insoluble drugs in liposomes prepared by the microencapsulation vesicle method,” Int. J. Pharm., vol. 298, no. 1, pp. 198–205, Jul. 2005, doi: 10.1016/j.ijpharm.2005.04.029.
[76] A. Parambath, Engineering of Biomaterials for Drug Delivery Systems: Beyond Polyethylene Glycol. 2018.
[77] R. Catania et al., “Functionalised liposomal formulations for delivery of antibiotic agents,” Access Microbiol., vol. 1, no. 1A, Mar. 2019, doi: 10.1099/acmi.ac2019.po0507.
[78] S. Zununi Vahed, R. Salehi, S. Davaran, and S. Sharifi, “Liposome-based drug co-delivery systems in cancer cells,” Mater. Sci. Eng. C, vol. 71, pp. 1327–1341, Feb. 2017, doi: 10.1016/j.msec.2016.11.073.
[79] A. Garu, G. Moku, S. K. Gulla, and A. Chaudhuri, “Genetic Immunization With In Vivo Dendritic Cell-targeting Liposomal DNA Vaccine Carrier Induces Long-lasting Antitumor Immune Response,” Mol. Ther., vol. 24, no. 2, pp. 385–397, Feb. 2016, doi: 10.1038/mt.2015.215.
[80] M. Muhaimin, A. Y. Chaerunisaa, M. K. Dewi, A. Khatib, and A. Hazrina, “The Toxicological Profile of Active Pharmaceutical Ingredients–Containing Nanoparticles: Classification, Mechanistic Pathways, and Health Implications,” Pharmaceuticals, vol. 18, no. 5, p. 703, May 2025, doi: 10.3390/ph18050703.
[81] M.-J. Chou et al., “Highly Efficient Intracellular Protein Delivery by Cationic Polyethyleneimine-Modified Gelatin Nanoparticles,” Materials (Basel)., vol. 11, no. 2, p. 301, Feb. 2018, doi: 10.3390/ma11020301.
[82] F. Zeeshan, T. Madheswaran, J. Panneerselvam, R. Taliyan, and P. Kesharwani, “Human Serum Albumin as Multifunctional Nanocarrier for Cancer Therapy,” J. Pharm. Sci., vol. 110, no. 9, pp. 3111–3117, Sep. 2021, doi: 10.1016/j.xphs.2021.05.001.
[83] M. Tarhini, H. Greige-Gerges, and A. Elaissari, “Protein-based nanoparticles: From preparation to encapsulation of active molecules,” Int. J. Pharm., vol. 522, no. 1–2, pp. 172–197, Apr. 2017, doi: 10.1016/j.ijpharm.2017.01.067.
[84] J. Mariam, S. Sivakami, and P. M. Dongre, “Albumin corona on nanoparticles – a strategic approach in drug delivery,” Drug Deliv., vol. 23, no. 8, pp. 2668–2676, Oct. 2016, doi: 10.3109/10717544.2015.1048488.
[85] H. Wartlick, B. Spänkuch-Schmitt, K. Strebhardt, J. Kreuter, and K. Langer, “Tumour cell delivery of antisense oligonuclceotides by human serum albumin nanoparticles,” J. Control. Release, vol. 96, no. 3, pp. 483–495, May 2004, doi: 10.1016/j.jconrel.2004.01.029.
[86] H. Choudhury, B. Gorain, M. Pandey, R. K. Khurana, and P. Kesharwani, “Strategizing biodegradable polymeric nanoparticles to cross the biological barriers for cancer targeting,” Int. J. Pharm., vol. 565, pp. 509–522, Jun. 2019, doi: 10.1016/j.ijpharm.2019.05.042.
[87] A. Kumari, S. K. Yadav, and S. C. Yadav, “Biodegradable polymeric nanoparticles based drug delivery systems,” Colloids Surfaces B Biointerfaces, vol. 75, no. 1, pp. 1–18, Jan. 2010, doi: 10.1016/j.colsurfb.2009.09.001.
[88] S. H. Akrawi et al., “Development and Optimization of Naringenin-Loaded Chitosan-Coated Nanoemulsion for Topical Therapy in Wound Healing,” Pharmaceutics, vol. 12, no. 9, p. 893, Sep. 2020, doi: 10.3390/pharmaceutics12090893.
[89] K. Anagnostou, M. Stylianakis, S. Michaleas, and A. Skouras, “Biodegradable nanomaterials,” in Nanomaterials for Clinical Applications, Elsevier, 2020, pp. 123–157. doi: 10.1016/B978-0-12-816705-2.00005-9.
[90] S. Niu et al., “A chitosan-based cascade-responsive drug delivery system for triple-negative breast cancer therapy,” J. Nanobiotechnology, vol. 17, no. 1, p. 95, Dec. 2019, doi: 10.1186/s12951-019-0529-4.
[91] J. Y. Yhee et al., “Effects of tumor microenvironments on targeted delivery of glycol chitosan nanoparticles,” J. Control. Release, vol. 267, pp. 223–231, Dec. 2017, doi: 10.1016/j.jconrel.2017.09.015.
[92] Z. Hou et al., “Both FA- and mPEG-conjugated chitosan nanoparticles for targeted cellular uptake and enhanced tumor tissue distribution,” Nanoscale Res. Lett., vol. 6, no. 1, p. 563, Dec. 2011, doi: 10.1186/1556-276X-6-563.
[93] M. Balduzzi, M. Diociaiuti, B. De Berardis, S. Paradisi, and L. Paoletti, “In vitro effects on macrophages induced by noncytotoxic doses of silica particles possibly relevant to ambient exposure,” Environ. Res., vol. 96, no. 1, pp. 62–71, Sep. 2004, doi: 10.1016/j.envres.2003.11.004.
[94] E.-J. Park and K. Park, “Oxidative stress and pro-inflammatory responses induced by silica nanoparticles in vivo and in vitro,” Toxicol. Lett., vol. 184, no. 1, pp. 18–25, Jan. 2009, doi: 10.1016/j.toxlet.2008.10.012.
[95] W. Lin, Y. Huang, X.-D. Zhou, and Y. Ma, “In vitro toxicity of silica nanoparticles in human lung cancer cells,” Toxicol. Appl. Pharmacol., vol. 217, no. 3, pp. 252–259, Dec. 2006, doi: 10.1016/j.taap.2006.10.004.
[96] L. Sun et al., “Cytotoxicity and mitochondrial damage caused by silica nanoparticles,” Toxicol. Vitr., vol. 25, no. 8, pp. 1619–1629, Dec. 2011, doi: 10.1016/j.tiv.2011.06.012.
[97] W. CHO et al., “Inflammatory mediators induced by intratracheal instillation of ultrafine amorphous silica particles,” Toxicol. Lett., vol. 175, no. 1–3, pp. 24–33, Dec. 2007, doi: 10.1016/j.toxlet.2007.09.008.
[98] M. Cho et al., “The impact of size on tissue distribution and elimination by single intravenous injection of silica nanoparticles,” Toxicol. Lett., vol. 189, no. 3, pp. 177–183, Sep. 2009, doi: 10.1016/j.toxlet.2009.04.017.
[99] H. Nishimori, M. Kondoh, K. Isoda, S. Tsunoda, Y. Tsutsumi, and K. Yagi, “Silica nanoparticles as hepatotoxicants,” Eur. J. Pharm. Biopharm., vol. 72, no. 3, pp. 496–501, Aug. 2009, doi: 10.1016/j.ejpb.2009.02.005.
[100] X.-F. Zhang, Z.-G. Liu, W. Shen, and S. Gurunathan, “Silver Nanoparticles: Synthesis, Characterization, Properties, Applications, and Therapeutic Approaches,” Int. J. Mol. Sci., vol. 17, no. 9, p. 1534, Sep. 2016, doi: 10.3390/ijms17091534.
[101] M. Auffan, J. Rose, J.-Y. Bottero, G. V. Lowry, J.-P. Jolivet, and M. R. Wiesner, “Towards a definition of inorganic nanoparticles from an environmental, health and safety perspective,” Nat. Nanotechnol., vol. 4, no. 10, pp. 634–641, Oct. 2009, doi: 10.1038/nnano.2009.242.
[102] H. J. Johnston, G. Hutchison, F. M. Christensen, S. Peters, S. Hankin, and V. Stone, “A review of the in vivo and in vitro toxicity of silver and gold particulates: Particle attributes and biological mechanisms responsible for the observed toxicity,” Crit. Rev. Toxicol., vol. 40, no. 4, pp. 328–346, Apr. 2010, doi: 10.3109/10408440903453074.
[103] J. Park et al., “Size dependent macrophage responses and toxicological effects of Ag nanoparticles,” Chem. Commun., vol. 47, no. 15, p. 4382, 2011, doi: 10.1039/c1cc10357a.
[104] K. W. Powers, S. C. Brown, V. B. Krishna, S. C. Wasdo, B. M. Moudgil, and S. M. Roberts, “Research Strategies for Safety Evaluation of Nanomaterials. Part VI. Characterization of Nanoscale Particles for Toxicological Evaluation,” Toxicol. Sci., vol. 90, no. 2, pp. 296–303, Apr. 2006, doi: 10.1093/toxsci/kfj099.
[105] S. Hirn et al., “Particle size-dependent and surface charge-dependent biodistribution of gold nanoparticles after intravenous administration,” Eur. J. Pharm. Biopharm., vol. 77, no. 3, pp. 407–416, Apr. 2011, doi: 10.1016/j.ejpb.2010.12.029.
[106] Y. Zhao, X. Sun, G. Zhang, B. G. Trewyn, I. I. Slowing, and V. S.-Y. Lin, “Interaction of Mesoporous Silica Nanoparticles with Human Red Blood Cell Membranes: Size and Surface Effects,” ACS Nano, vol. 5, no. 2, pp. 1366–1375, Feb. 2011, doi: 10.1021/nn103077k.
[107] V. Rabolli et al., “Influence of size, surface area and microporosity on the in vitro cytotoxic activity of amorphous silica nanoparticles in different cell types,” Nanotoxicology, vol. 4, no. 3, pp. 307–318, Sep. 2010, doi: 10.3109/17435390.2010.482749.
[108] C. Lopez-Chaves, J. Soto-Alvaredo, M. Montes-Bayon, J. Bettmer, J. Llopis, and C. Sanchez-Gonzalez, “Gold nanoparticles: Distribution, bioaccumulation and toxicity. In vitro and in vivo studies,” Nanomedicine Nanotechnology, Biol. Med., vol. 14, no. 1, pp. 1–12, Jan. 2018, doi: 10.1016/j.nano.2017.08.011.
[109] E. A. Morsy, A. M. Hussien, M. A. Ibrahim, K. Y. Farroh, and E. I. Hassanen, “Cytotoxicity and Genotoxicity of Copper oxide Nanoparticles in chickens,” Biol. Trace Elem. Res., vol. 199, no. 12, pp. 4731–4745, Dec. 2021, doi: 10.1007/s12011-021-02595-4.
[110] S. Kim and D. Ryu, “Silver nanoparticle‐induced oxidative stress, genotoxicity and apoptosis in cultured cells and animal tissues,” J. Appl. Toxicol., vol. 33, no. 2, pp. 78–89, Feb. 2013, doi: 10.1002/jat.2792.
[111] X. Zhang et al., “Continuous graphene and carbon nanotube based high flexible and transparent pressure sensor arrays,” Nanotechnology, vol. 26, no. 11, p. 115501, Mar. 2015, doi: 10.1088/0957-4484/26/11/115501.
[112] C. Grabinski, S. Hussain, K. Lafdi, L. Braydich-Stolle, and J. Schlager, “Effect of particle dimension on biocompatibility of carbon nanomaterials,” Carbon N. Y., vol. 45, no. 14, pp. 2828–2835, Nov. 2007, doi: 10.1016/j.carbon.2007.08.039.
[113] J.-R. Gurr, A. S. S. Wang, C.-H. Chen, and K.-Y. Jan, “Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells,” Toxicology, vol. 213, no. 1–2, pp. 66–73, Sep. 2005, doi: 10.1016/j.tox.2005.05.007.
[114] R. Bacchetta, N. Santo, I. Valenti, D. Maggioni, M. Longhi, and P. Tremolada, “Comparative toxicity of three differently shaped carbon nanomaterials on Daphnia magna : does a shape effect exist?,” Nanotoxicology, vol. 12, no. 3, pp. 201–223, Mar. 2018, doi: 10.1080/17435390.2018.1430258.
[115] A. Verma and F. Stellacci, “Effect of Surface Properties on Nanoparticle–Cell Interactions,” Small, vol. 6, no. 1, pp. 12–21, Jan. 2010, doi: 10.1002/smll.200901158.
[116] J. A. Champion and S. Mitragotri, “Role of target geometry in phagocytosis,” Proc. Natl. Acad. Sci., vol. 103, no. 13, pp. 4930–4934, Mar. 2006, doi: 10.1073/pnas.0600997103.
[117] M. Ferrari, “Beyond drug delivery,” Nat. Nanotechnol., vol. 3, no. 3, pp. 131–132, Mar. 2008, doi: 10.1038/nnano.2008.46.
[118] W. Hu et al., “Protein Corona-Mediated Mitigation of Cytotoxicity of Graphene Oxide,” ACS Nano, vol. 5, no. 5, pp. 3693–3700, May 2011, doi: 10.1021/nn200021j.
[119] J. PetkoviĆ et al., “DNA damage and alterations in expression of DNA damage responsive genes induced by TiO 2 nanoparticles in human hepatoma HepG2 cells,” Nanotoxicology, vol. 5, no. 3, pp. 341–353, Sep. 2011, doi: 10.3109/17435390.2010.507316.
[120] N. B. Abramenko, T. B. Demidova, Е. V. Abkhalimov, B. G. Ershov, E. Y. Krysanov, and L. M. Kustov, “Ecotoxicity of different-shaped silver nanoparticles: Case of zebrafish embryos,” J. Hazard. Mater., vol. 347, pp. 89–94, Apr. 2018, doi: 10.1016/j.jhazmat.2017.12.060.
[121] C. Carnovale, G. Bryant, R. Shukla, and V. Bansal, “Identifying Trends in Gold Nanoparticle Toxicity and Uptake: Size, Shape, Capping Ligand, and Biological Corona,” ACS Omega, vol. 4, no. 1, pp. 242–256, Jan. 2019, doi: 10.1021/acsomega.8b03227.
[122] H. Zhou et al., “Gold nanoparticles impair autophagy flux through shape-dependent endocytosis and lysosomal dysfunction,” J. Mater. Chem. B, vol. 6, no. 48, pp. 8127–8136, 2018, doi: 10.1039/C8TB02390E.
[123] S. Sánchez-Paradinas et al., “Enhanced cytotoxic activity of bile acid cisplatin derivatives by conjugation with gold nanoparticles,” J. Inorg. Biochem., vol. 131, pp. 8–11, Feb. 2014, doi: 10.1016/j.jinorgbio.2013.10.021.
[124] J. Muller et al., “Respiratory toxicity of multi-wall carbon nanotubes,” Toxicol. Appl. Pharmacol., vol. 207, no. 3, pp. 221–231, Sep. 2005, doi: 10.1016/j.taap.2005.01.008.
[125] L. Li, T. Liu, C. Fu, L. Tan, X. Meng, and H. Liu, “Biodistribution, excretion, and toxicity of mesoporous silica nanoparticles after oral administration depend on their shape,” Nanomedicine Nanotechnology, Biol. Med., vol. 11, no. 8, pp. 1915–1924, Nov. 2015, doi: 10.1016/j.nano.2015.07.004.
[126] Y.-K. Lai et al., “TiO2 nanotube platforms for smart drug delivery: a review,” Int. J. Nanomedicine, vol. Volume 11, pp. 4819–4834, Sep. 2016, doi: 10.2147/IJN.S108847.
[127] M. Anderson and A. Omri, “The Effect of Different Lipid Components on the In Vitro Stability and Release Kinetics of Liposome Formulations,” Drug Deliv., vol. 11, no. 1, pp. 33–39, Jan. 2004, doi: 10.1080/10717540490265243.
[128] T. J. Brunner et al., “In Vitro Cytotoxicity of Oxide Nanoparticles: Comparison to Asbestos, Silica, and the Effect of Particle Solubility,” Environ. Sci. Technol., vol. 40, no. 14, pp. 4374–4381, Jul. 2006, doi: 10.1021/es052069i.
[129] M. R. Larsen, T. E. Thingholm, O. N. Jensen, P. Roepstorff, and T. J. D. Jørgensen, “Highly Selective Enrichment of Phosphorylated Peptides from Peptide Mixtures Using Titanium Dioxide Microcolumns,” Mol. Cell. Proteomics, vol. 4, no. 7, pp. 873–886, Jul. 2005, doi: 10.1074/mcp.T500007-MCP200.
[130] J. Sund, H. Alenius, M. Vippola, K. Savolainen, and A. Puustinen, “Proteomic Characterization of Engineered Nanomaterial–Protein Interactions in Relation to Surface Reactivity,” ACS Nano, vol. 5, no. 6, pp. 4300–4309, Jun. 2011, doi: 10.1021/nn101492k.
[131] B. Y. S. Kim, J. T. Rutka, and W. C. W. Chan, “Nanomedicine,” N. Engl. J. Med., vol. 363, no. 25, pp. 2434–2443, Dec. 2010, doi: 10.1056/NEJMra0912273.
[132] Y. Liu et al., “Intracellular dynamics of cationic and anionic polystyrene nanoparticles without direct interaction with mitotic spindle and chromosomes,” Biomaterials, vol. 32, no. 32, pp. 8291–8303, Nov. 2011, doi: 10.1016/j.biomaterials.2011.07.037.
[133] A. M. Alkilany and C. J. Murphy, “Toxicity and cellular uptake of gold nanoparticles: what we have learned so far?,” J. Nanoparticle Res., vol. 12, no. 7, pp. 2313–2333, Sep. 2010, doi: 10.1007/s11051-010-9911-8.
[134] T. Coccini et al., “Effects of water-soluble functionalized multi-walled carbon nanotubes examined by different cytotoxicity methods in human astrocyte D384 and lung A549 cells,” Toxicology, vol. 269, no. 1, pp. 41–53, Feb. 2010, doi: 10.1016/j.tox.2010.01.005.
[135] S. K. Misra, A. Dybowska, D. Berhanu, S. N. Luoma, and E. Valsami-Jones, “The complexity of nanoparticle dissolution and its importance in nanotoxicological studies,” Sci. Total Environ., vol. 438, pp. 225–232, Nov. 2012, doi: 10.1016/j.scitotenv.2012.08.066.
[136] L. C. Kumar CSSR, Hormes J, Nanofabrication Towards Biomedical Applications: Techniques, Tools, Applications, and Impact. Nanofabrication Towards Biomedical Applications: Techniques, Tools, Applications, and Impact. Wiley, 2005. doi: 10.1002/3527603476.
[137] C. Bantz et al., “The surface properties of nanoparticles determine the agglomeration state and the size of the particles under physiological conditions,” Beilstein J. Nanotechnol., vol. 5, pp. 1774–1786, Oct. 2014, doi: 10.3762/bjnano.5.188.
[138] P. WICK et al., “The degree and kind of agglomeration affect carbon nanotube cytotoxicity,” Toxicol. Lett., vol. 168, no. 2, pp. 121–131, Jan. 2007, doi: 10.1016/j.toxlet.2006.08.019.
[139] J. M. Zook, R. I. MacCuspie, L. E. Locascio, M. D. Halter, and J. T. Elliott, “Stable nanoparticle aggregates/agglomerates of different sizes and the effect of their size on hemolytic cytotoxicity,” Nanotoxicology, vol. 5, no. 4, pp. 517–530, Dec. 2011, doi: 10.3109/17435390.2010.536615.
[140] C. Egbuna, “Oxidative Stress and Nutrition,” Trop. J. Appl. Nat. Sci., vol. 2, no. 1, pp. 110–116, Oct. 2017, doi: 10.25240/TJANS.2017.2.1.19.
[141] J. Ifemeje et al., “Determination of Total Protein, Superoxide Dismutase, Catalase Activity and Lipid Peroxidation in Soil Macro-fauna (Earthworm) from Onitsha Municipal Open Waste Dump,” J. Sci. Res. Reports, vol. 6, no. 5, pp. 394–403, Jan. 2015, doi: 10.9734/JSRR/2015/12552.
[142] E. Biazar et al., “Nanotoxicology and nanoparticle safety in biomedical designs,” Int. J. Nanomedicine, p. 1117, May 2011, doi: 10.2147/IJN.S16603.
[143] J. K. Tee, C. N. Ong, B. H. Bay, H. K. Ho, and D. T. Leong, “Oxidative stress by inorganic nanoparticles,” WIREs Nanomedicine and Nanobiotechnology, vol. 8, no. 3, pp. 414–438, May 2016, doi: 10.1002/wnan.1374.
[144] A. Nel, T. Xia, L. Mädler, and N. Li, “Toxic Potential of Materials at the Nanolevel,” Science (80-. )., vol. 311, no. 5761, pp. 622–627, Feb. 2006, doi: 10.1126/science.1114397.
[145] N. D. Magnani, T. Marchini, V. Calabró, S. Alvarez, and P. Evelson, “Role of Mitochondria in the Redox Signaling Network and Its Outcomes in High Impact Inflammatory Syndromes,” Front. Endocrinol. (Lausanne)., vol. 11, Sep. 2020, doi: 10.3389/fendo.2020.568305.
[146] B. Lipinski, “Hydroxyl Radical and Its Scavengers in Health and Disease,” Oxid. Med. Cell. Longev., vol. 2011, pp. 1–9, 2011, doi: 10.1155/2011/809696.
[147] B. Halliwell, “Superoxide‐dependent formation of hydroxyl radicals in the presence of iron chelates,” FEBS Lett., vol. 92, no. 2, pp. 321–326, Aug. 1978, doi: 10.1016/0014-5793(78)80779-0.
[148] V. S. Radhakrishnan, S. P. Dwivedi, M. H. Siddiqui, and T. Prasad, “In vitro studies on oxidative stress-independent, Ag nanoparticles-induced cell toxicity of Candida albicans, an opportunistic pathogen,” Int. J. Nanomedicine, vol. Volume 13, pp. 91–96, Mar. 2018, doi: 10.2147/IJN.S125010.
[149] M. I. Setyawati, X. Yuan, J. Xie, and D. T. Leong, “The influence of lysosomal stability of silver nanomaterials on their toxicity to human cells,” Biomaterials, vol. 35, no. 25, pp. 6707–6715, Aug. 2014, doi: 10.1016/j.biomaterials.2014.05.007.
[150] D. Mateo, P. Morales, A. Ávalos, and A. I. Haza, “Oxidative stress contributes to gold nanoparticle-induced cytotoxicity in human tumor cells,” Toxicol. Mech. Methods, vol. 24, no. 3, pp. 161–172, Mar. 2014, doi: 10.3109/15376516.2013.869783.
[151] M. Enea, E. Pereira, M. Peixoto de Almeida, A. M. Araújo, M. de L. Bastos, and H. Carmo, “Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells,” Nanomaterials, vol. 10, no. 5, p. 995, May 2020, doi: 10.3390/nano10050995.
[152] K. M. Ramkumar et al., “Oxidative stress-mediated cytotoxicity and apoptosis induction by TiO2 nanofibers in HeLa cells,” Eur. J. Pharm. Biopharm., vol. 81, no. 2, pp. 324–333, Jun. 2012, doi: 10.1016/j.ejpb.2012.02.013.
[153] R. Hu et al., “Molecular mechanism of hippocampal apoptosis of mice following exposure to titanium dioxide nanoparticles,” J. Hazard. Mater., vol. 191, no. 1–3, pp. 32–40, Jul. 2011, doi: 10.1016/j.jhazmat.2011.04.027.
[154] L. Ma et al., “Oxidative stress in the brain of mice caused by translocated nanoparticulate TiO2 delivered to the abdominal cavity,” Biomaterials, vol. 31, no. 1, pp. 99–105, Jan. 2010, doi: 10.1016/j.biomaterials.2009.09.028.
[155] H. Liu, L. Ma, J. Liu, J. Zhao, J. Yan, and F. Hong, “Toxicity of nano-anatase TiO 2 to mice: Liver injury, oxidative stress,” Toxicol. Environ. Chem., vol. 92, no. 1, pp. 175–186, Jan. 2010, doi: 10.1080/02772240902732530.
[156] T. C. Long et al., “Nanosize Titanium Dioxide Stimulates Reactive Oxygen Species in Brain Microglia and Damages Neurons in Vitro,” Environ. Health Perspect., vol. 115, no. 11, pp. 1631–1637, Nov. 2007, doi: 10.1289/ehp.10216.
[157] C. Guo et al., “Silica nanoparticles induce oxidative stress, inflammation, and endothelial dysfunction in vitro via activation of the MAPK/Nrf2 pathway and nuclear factor-κB signaling,” Int. J. Nanomedicine, p. 1463, Feb. 2015, doi: 10.2147/IJN.S76114.
[158] D. Boraschi et al., “Nanoparticles and innate immunity: new perspectives on host defence,” Semin. Immunol., vol. 34, pp. 33–51, Dec. 2017, doi: 10.1016/j.smim.2017.08.013.
[159] Aguilar ZP, Nanomaterials for Medical Applications. Elsevier, 2013. doi: 10.1016/C2010-0-65569-6.
[160] C. D. Walkey, J. B. Olsen, H. Guo, A. Emili, and W. C. W. Chan, “Nanoparticle Size and Surface Chemistry Determine Serum Protein Adsorption and Macrophage Uptake,” J. Am. Chem. Soc., vol. 134, no. 4, pp. 2139–2147, Feb. 2012, doi: 10.1021/ja2084338.
[161] L. Kostura, D. L. Kraitchman, A. M. Mackay, M. F. Pittenger, and J. W. M. Bulte, “Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis,” NMR Biomed., vol. 17, no. 7, pp. 513–517, Nov. 2004, doi: 10.1002/nbm.925.
[162] Y.-C. Chen et al., “The inhibitory effect of superparamagnetic iron oxide nanoparticle (Ferucarbotran) on osteogenic differentiation and its signaling mechanism in human mesenchymal stem cells,” Toxicol. Appl. Pharmacol., vol. 245, no. 2, pp. 272–279, Jun. 2010, doi: 10.1016/j.taap.2010.03.011.
[163] D. A. Kedziorek et al., “Gene expression profiling reveals early cellular responses to intracellular magnetic labeling with superparamagnetic iron oxide nanoparticles,” Magn. Reson. Med., vol. 63, no. 4, pp. 1031–1043, Apr. 2010, doi: 10.1002/mrm.22290.
[164] J. Puppi, R. R. Mitry, M. Modo, A. Dhawan, K. Raja, and R. D. Hughes, “Use of a Clinically Approved Iron Oxide MRI Contrast Agent to Label Human Hepatocytes,” Cell Transplant., vol. 20, no. 6, pp. 963–976, Jul. 2011, doi: 10.3727/096368910X543367.
[165] L. Wang, C. Hu, and L. Shao, “The antimicrobial activity of nanoparticles: present situation and prospects for the future,” Int. J. Nanomedicine, vol. Volume 12, pp. 1227–1249, Feb. 2017, doi: 10.2147/IJN.S121956.
[166] M. Poirier, J. Simard, F. Antoine, and D. Girard, “Interaction between silver nanoparticles of 20 nm (AgNP 20 ) and human neutrophils: induction of apoptosis and inhibition of de novo protein synthesis by AgNP 20 aggregates,” J. Appl. Toxicol., vol. 34, no. 4, pp. 404–412, Apr. 2014, doi: 10.1002/jat.2956.
[167] M. K. Dewi, A. Y. Chaerunisaa, M. Muhaimin, and I. M. Joni, “Improved Activity of Herbal Medicines through Nanotechnology,” Nanomaterials, vol. 12, no. 22, p. 4073, Nov. 2022, doi: 10.3390/nano12224073.
[168] W. G. Kreyling, M. Semmler-Behnke, and W. Möller, “Health implications of nanoparticles,” J. Nanoparticle Res., vol. 8, no. 5, pp. 543–562, Nov. 2006, doi: 10.1007/s11051-005-9068-z.
[169] V. Sharma, R. K. Shukla, N. Saxena, D. Parmar, M. Das, and A. Dhawan, “DNA damaging potential of zinc oxide nanoparticles in human epidermal cells,” Toxicol. Lett., vol. 185, no. 3, pp. 211–218, Mar. 2009, doi: 10.1016/j.toxlet.2009.01.008.
[170] M. Muhaimin, U. Lestari, R. Hirzan, and A. Y. Chaerunisaa, “The potential of medicinal plants in tuberculosis treatment: Indigenous plants used by the Anak Dalam tribe of Jambi, Indonesia,” South African J. Bot., vol. 180, pp. 688–709, May 2025, doi: 10.1016/j.sajb.2025.03.046.
[171] M. Muhaimin, A. Y. Chaerunisaa, and R. Bodmeier, “Impact of dispersion time interval and particle size on release profiles of propranolol HCl and carbamazepines from microparticle blends system,” Sci. Rep., vol. 12, no. 1, p. 10360, Jun. 2022, doi: 10.1038/s41598-022-14678-w.
[172] S. Nurhasanah, Y. Iskandar, M. Muhaimin, A. Hazrina, R. Hirzan, and W. Syahri, “Polymer Type Effect On Premna Serratifolia Extract-Loaded Microparticles Preparation By Solvent Evaporation Method With Single Emulsion System,” Int. J. Appl. Pharm., pp. 250–256, Jul. 2024, doi: 10.22159/ijap.2024v16i4.50173.
[173] T. Rostinawati, M. Muhaimin, A. Y. Chaerunisaa, and A. Hazrina, “Development Of Casticin-Loaded Ethyl Cellulose Microparticles By Solvent Evaporation Method With Single Emulsion System,” Int. J. Appl. Pharm., pp. 235–240, Nov. 2023, doi: 10.22159/ijap.2023v15i6.48758.
[174] U. CDC-NIOSH, “Current Intelligence Bulletin 63: occupational exposure to titanium dioxide.,” vol. 2011–160, 2011.
[175] OECD, Guidance Document For The Testing of Dissolution and Dispersion Stability of Nanomaterials and The Use of The Data For Further Environmental Testing And Assessment Strategies. Series on Testing and Assessment No. 318. 2020.
[176] ISO, “ISO/TR 16197:2014 - Nanotechnologies — Compilation and description of toxicological screening methods for manufactured nanomaterials.,” 2014.
[177] EMA, “Reflection Paper on Nanotechnology-based Medicinal Products for Human Use.,” 2021.
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