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Review

Safety assessment of nanoparticles for drug delivery by means of classic in vitro assays and beyond

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Pages 1545-1558 | Received 12 Apr 2016, Accepted 03 Jun 2016, Published online: 29 Jun 2016

References

  • Couvreur P, Kante B, Lenaerts V, et al. Tissue distribution of antitumor drugs associated with polyalkylcyanoacrylate nanoparticles. J Pharm Sci. 1980;69:199–202.
  • Forssen EA, Tökès ZA. Use of anionic liposomes for the reduction of chronic doxorubicin-induced cardiotoxicity. Proc Natl Acad Sci USA. 1981;78:1873–1877.
  • Barenholz Y (Chezy). Doxil® — The first FDA-approved nano-drug: lessons learned. J Controlled Release. 2012;160:117–134.
  • Donaldson K, Stone V, Tran CL, et al. Nanotoxicology. Occup Environ Med. 2004;61:727–728.
  • Dhawan A, Sharma V. Toxicity assessment of nanomaterials: methods and challenges. Anal Bioanal Chem. 2010;398:589–605.
  • Guadagnini R, Kenzaoui BH, Walker L, et al. Toxicity screenings of nanomaterials: challenges due to interference with assay processes and components of classic in vitro tests. Nanotoxicology. 2015;9:13–24.
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63.
  • Berridge MV, Herst PM, Tan AS. Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev. 2005;11:127–152.
  • O’Brien J, Wilson I, Orton T, et al. Investigation of the alamar blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur J Biochem. 2000;267:5421–5426.
  • Bradbury DA, Simmons TD, Slater KJ, et al. Measurement of the ADP:ATP ratio in human leukaemic cell lines can be used as an indicator of cell viability, necrosis and apoptosis. J Immunol Methods. 2000;240:79–92.
  • Borenfreund E, Puerner JA. A simple quantitative procedure using monolayer cultures for cytotoxicity assays (HTD/NR-90). J Tissue Cult Methods. 1985;9:7–9.
  • Repetto G, Del Peso A, Zurita JL. Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nat Protoc. 2008;3:1125–1131.
  • Lichtenfels R, Biddison WE, Schulz H, et al. CARE-LASS (calcein-release-assay), an improved fluorescence-based test system to measure cytotoxic T lymphocyte activity. J Immunol Methods. 1994;172:227–239.
  • Papadopoulos NG, Dedoussis GVZ, Spanakos G, et al. An improved fluorescence assay for the determination of lymphocyte-mediated cytotoxicity using flow cytometry. J Immunol Methods. 1994;177:101–111.
  • Burd JF, Usategui-Gomez M. A colorimetric assay for serum lactate dehydrogenase. Clin Chim Acta. 1973;46:223–227.
  • Sohaebuddin SK, Thevenot PT, Baker D, et al. Nanomaterial cytotoxicity is composition, size, and cell type dependent. Part Fibre Toxicol. 2010;7:22.
  • Wrobel K, Claudio E, Segade F, et al. Measurement of cytotoxicity by propidium iodide staining of target cell DNA: application to the quantification of murine TNF-α. J Immunol Methods. 1996;189:243–249.
  • Tennant JR. Evaluation of the trypan blue technique for determination of cell viability. Transplantation. 1964;2:685–694.
  • Elia MC, Storer RD, Harmon LS, et al. Cytotoxicity as measured by trypan blue as a potentially confounding variable in the in vitro alkaline elution/rat hepatocyte assay. Mutat Res Mutagen Relat Subj. 1993;291:193–205.
  • Doktorovova S, Souto EB, Silva AM. Nanotoxicology applied to solid lipid nanoparticles and nanostructured lipid carriers – A systematic review of in vitro data. Eur J Pharm Biopharm. 2014;87:1–18.
  • Duan J, Yu Y, Yu Y, et al. Silica nanoparticles enhance autophagic activity, disturb endothelial cell homeostasis and impair angiogenesis. Part Fibre Toxicol. 2014;11:11–50.
  • Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992;119:493–501.
  • Labat-Moleur F, Guillermet C, Lorimier P, et al. TUNEL apoptotic cell detection in tissue sections: critical evaluation and improvement. J Histochem Cytochem. 1998;46:327–334.
  • Martin SJ, Reutelingsperger CP, McGahon AJ, et al. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med. 1995;182:1545–1556.
  • Duque A, Rakic P. Different effects of BrdU and 3H-thymidine incorporation into DNA on cell proliferation, position and fate. J Neurosci Off J Soc Neurosci. 2011;31:15205–15217.
  • Dragan AI, Casas-Finet JR, Bishop ES, et al. Characterization of PicoGreen Interaction with dsDNA and the origin of its fluorescence enhancement upon Binding. Biophys J. 2010;99:3010–3019.
  • Singh NP, McCoy MT, Tice RR, et al. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988;175:184–191.
  • Ferraro D, Anselmi-Tamburini U, Tredici IG, et al. Overestimation of nanoparticles-induced DNA damage determined by the comet assay. Nanotoxicology. 2016;10:861–870.
  • Rogakou EP, Pilch DR, Orr AH, et al. Induce Histone H2AX Phosphorylation on Serine 139. J Biol Chem. 1998;273:5858–5868.
  • Garcia-Canton C, Anadon A, Meredith C. Assessment of the in vitro γH2AX assay by high content screening as a novel genotoxicity test. Mutat Res Toxicol Environ Mutagen. 2013;757:158–166.
  • Fenech M, Kirsch-Volders M, Natarajan AT, et al. Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis. 2011;26:125–132.
  • Elhajouji A, Cunha M, Kirsch-Volders M. Spindle poisons can induce polyploidy by mitotic slippage and micronucleate mononucleates in the cytokinesis-block assay. Mutagenesis. 1998;13:193–198.
  • Perry P, Wolff S. New Giemsa method for the differential staining of sister chromatids. Nature. 1974;251:156–158.
  • Val S, Hussain S, Boland S, et al. Carbon black and titanium dioxide nanoparticles induce pro-inflammatory responses in bronchial epithelial cells: need for multiparametric evaluation due to adsorption artifacts. Inhal Toxicol. 2009;21:115–122.
  • Stoehr LC, Endes C, Radauer-Preiml I, et al. Assessment of a panel of interleukin-8 reporter lung epithelial cell lines to monitor the pro-inflammatory response following zinc oxide nanoparticle exposure under different cell culture conditions. Part Fibre Toxicol. 2015;12:29.
  • Jason J, Larned J. Single-cell cytokine profiles in normal humans: comparison of flow cytometric reagents and stimulation protocols. J Immunol Methods. 1997;207:13–22.
  • Fisher JM, Wrighton SA, Calamia JC, et al. Midazolam metabolism by modified Caco-2 monolayers: effects of extracellular protein binding. J Pharmacol Exp Ther. 1999;289:1143–1150.
  • Doshi U, Li AP. Luciferin IPA–based higher throughput human hepatocyte screening assays for CYP3A4 inhibition and induction. J Biomol Screen. 2011;16:903–909.
  • Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82:70–77.
  • Sebastià J, Cristòfol R, Martín M, et al. Evaluation of fluorescent dyes for measuring intracellular glutathione content in primary cultures of human neurons and neuroblastoma SH-SY5Y. Cytom Part J Int Soc Anal Cytol. 2003;51:16–25.
  • Zhang X, Gao F. Imaging mitochondrial reactive oxygen species with fluorescent probes: current applications and challenges. Free Radic Res. 2015;49:374–382.
  • Aranda A, Sequedo L, Tolosa L, et al. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay: a quantitative method for oxidative stress assessment of nanoparticle-treated cells. Toxicol In Vitro. 2013;27:954–963.
  • Kalyanaraman B, Darley-Usmar V, Davies KJA, et al. Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations. Free Radic Biol Med. 2012;52:1–6.
  • Ridnour LA, Sim JE, Hayward MA, et al. A spectrophotometric method for the direct detection and quantitation of nitric oxide, nitrite, and nitrate in cell culture media. Anal Biochem. 2000;281:223–229.
  • Tenzer S, Docter D, Kuharev J, et al. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nat Nanotechnol. 2013;8:772–781.
  • Jones CF, Grainger DW. In vitro assessments of nanomaterial toxicity. Adv Drug Deliv Rev. 2009;61:438–456.
  • Shetab Boushehri MA, Lamprecht A. Nanoparticles as drug carriers: current issues with in vitro testing. Nanomed. 2015;10:3213–3230.
  • Joris F, Manshian BB, Peynshaert K, et al. Assessing nanoparticle toxicity in cell-based assays: influence of cell culture parameters and optimized models for bridging the in vitro–in vivo gap. Chem Soc Rev. 2013;42:8339.
  • Kroemer G, Galluzzi L, Vandenabeele P, et al. Classification of cell death: recommendations of the nomenclature committee on cell death 2009. Cell Death Differ. 2008;16:3–11.
  • Stepanenko AA, Dmitrenko VV. Pitfalls of the MTT assay: direct and off-target effects of inhibitors can result in over/underestimation of cell viability. Gene. 2015;574:193–203.
  • Tasdemir E, Maiuri MC, Galluzzi L, et al. Regulation of autophagy by cytoplasmic p53. Nat Cell Biol. 2008;10:676–687.
  • Holló Z, Homolya L, Davis CW, et al. Calcein accumulation as a fluorometric functional assay of the multidrug transporter. Biochim Biophys Acta BBA - Biomembr. 1994;1191:384–388.
  • Han X, Gelein R, Corson N, et al. Validation of an LDH assay for assessing nanoparticle toxicity. Toxicology. 2011;287:99–104.
  • Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell. 2004;116:205–219.
  • Chen M, von Mikecz A. Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. Exp Cell Res. 2005;305:51–62.
  • Singh N, Manshian B, Jenkins GJS, et al. NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials. 2009;30:3891–3914.
  • Schins RPF, Knaapen AM. Genotoxicity of poorly soluble particles. Inhal Toxicol. 2007;19(Suppl 1):189–198.
  • Jugan M-L, Barillet S, Simon-Deckers A, et al. Titanium dioxide nanoparticles exhibit genotoxicity and impair DNA repair activity in A549 cells. Nanotoxicology. 2012;6:501–513.
  • Lopes MA, Abrahim BA, Cabral LM, et al. Intestinal absorption of insulin nanoparticles: contribution of M cells. Nanomedicine Nanotechnol Biol Med. 2014;10:1139–1151.
  • Owens III DE, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2006;307:93–102.
  • Toebak MJ, De Rooij J, Moed H, et al. Differential suppression of dendritic cell cytokine production by anti-inflammatory drugs. Br J Dermatol. 2008;158:225–233.
  • Nel AE, Mädler L, Velegol D, et al. Understanding biophysicochemical interactions at the nano–bio interface. Nat Mater. 2009;8:543–557.
  • Gibson GG, Plant NJ, Swales KE, et al. Receptor-dependent transcriptional activation of cytochrome P4503A genes: induction mechanisms, species differences and interindividual variation in man. Xenobiotica. 2002;32:165–206.
  • Fu C, Liu T, Li L, et al. The absorption, distribution, excretion and toxicity of mesoporous silica nanoparticles in mice following different exposure routes. Biomaterials. 2013;34:2565–2575.
  • Winterbourn CC. Reconciling the chemistry and biology of reactive oxygen species. Nat Chem Biol. 2008;4:278–286.
  • Babior BM. Oxidants from phagocytes: agents of defense and destruction. Blood. 1984;64:959–966.
  • Xia T, Kovochich M, Brant J, et al. Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Lett. 2006;6:1794–1807.
  • Bogdan C. Nitric oxide and the immune response. Nat Immunol. 2001;2:907–916.
  • Oberdörster G, Oberdörster E, Oberdörster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect. 2005;113:823–839.
  • Tammam SN, Azzazy HME, Lamprecht A. Biodegradable particulate carrier formulation and tuning for targeted drug delivery. J Biomed Nanotechnol. 2015;11:555–577.
  • Grabowski N, Hillaireau H, Vergnaud J, et al. Toxicity of surface-modified PLGA nanoparticles toward lung alveolar epithelial cells. Int J Pharm. 2013;454:686–694.
  • Grabowski N, Hillaireau H, Vergnaud J, et al. Surface coating mediates the toxicity of polymeric nanoparticles towards human-like macrophages. Int J Pharm. 2015;482:75–83.
  • Kazimirova A, Magdolenova Z, Barancokova M, et al. Genotoxicity testing of PLGA–PEO nanoparticles in TK6 cells by the comet assay and the cytokinesis-block micronucleus assay. Mutat Res Toxicol Environ Mutagen. 2012;748:42–47.
  • Calarco A, Bosetti M, Margarucci S, et al. The genotoxicity of PEI-based nanoparticles is reduced by acetylation of polyethylenimine amines in human primary cells. Toxicol Lett. 2013;218:10–17.
  • Guadagnini R, Moreau K, Hussain S, et al. Toxicity evaluation of engineered nanoparticles for medical applications using pulmonary epithelial cells. Nanotoxicology. 2015;9(Suppl 1):25–32.
  • Singh RP, Ramarao P. Accumulated polymer degradation products as effector molecules in cytotoxicity of polymeric nanoparticles. Toxicol Sci. 2013;136:131–143.
  • Al-Hallak KMHD, Azarmi S, Anwar-Mohamed A, et al. Secondary cytotoxicity mediated by alveolar macrophages: a contribution to the total efficacy of nanoparticles in lung cancer therapy? Eur J Pharm Biopharm. 2010;76:112–119.
  • Loh JW, Yeoh G, Saunders M, et al. Uptake and cytotoxicity of chitosan nanoparticles in human liver cells. Toxicol Appl Pharmacol. 2010;249:148–157.
  • Kaminskas LM, Kelly BD, McLeod VM, et al. Characterisation and tumour targeting of PEGylated polylysine dendrimers bearing doxorubicin via a pH labile linker. J Controlled Release. 2011;152:241–248.
  • Al Zaki A, Hui JZ, Higbee E, et al. Biodistribution, clearance, and toxicology of polymeric micelles loaded with 0.9 or 5 nm gold nanoparticles. J Biomed Nanotechnol. 2015;11:1836–1846.
  • Ensign LM, Cone R, Hanes J. Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers. Adv Drug Deliv Rev. 2012;64:557–570.
  • Niebel W, Walkenbach K, Béduneau A, et al. Nanoparticle-based clodronate delivery mitigates murine experimental colitis. J Controlled Release. 2012;160:659–665.
  • Eidi H, Joubert O, Attik G, et al. Cytotoxicity assessment of heparin nanoparticles in NR8383 macrophages. Int J Pharm. 2010;396:156–165.
  • Eidi H, Joubert O, Némos C, et al. Drug delivery by polymeric nanoparticles induces autophagy in macrophages. Int J Pharm. 2012;422:495–503.
  • Ronzani C, Safar R, Diab R, et al. Viability and gene expression responses to polymeric nanoparticles in human and rat cells. Cell Biol Toxicol. 2014;30:137–146.
  • Safar R, Ronzani C, Diab R, et al. Human monocyte response to S-nitrosoglutathione-loaded nanoparticles: uptake, viability, and transcriptome. Mol Pharm. 2015;12:554–561.
  • Sadekar S, Ghandehari H. Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery. Adv Drug Deliv Rev. 2012;64:571–588.
  • Akbarzadeh A, Rezaei-Sadabady R, Davaran S, et al. Liposome: classification, preparation, and applications. Nanoscale Res Lett. 2013;8:102.
  • Soenen SJH, Brisson AR, De Cuyper M. Addressing the problem of cationic lipid-mediated toxicity: the magnetoliposome model. Biomaterials. 2009;30:3691–3701.
  • Bartneck M, Peters FM, Warzecha KT, et al. Liposomal encapsulation of dexamethasone modulates cytotoxicity, inflammatory cytokine response, and migratory properties of primary human macrophages. Nanomedicine Nanotechnol Biol Med. 2014;10:1209–1220.
  • Battaglia L, Gallarate M. Lipid nanoparticles: state of the art, new preparation methods and challenges in drug delivery. Expert Opin Drug Deliv. 2012;9:497–508.
  • Orlando A, Re F, Sesana S, et al. Effect of nanoparticles binding β-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages. Int J Nanomedicine. 2013;8:1335–1347.
  • Jaganathan H, Godin B. Biocompatibility assessment of si-based nano- and micro-particles. Adv Drug Deliv Rev. 2012;64:1800–1819.
  • Goornavar V, Biradar S, Ezeagwu C, et al. Toxicity of raw and purified single-walled carbon nanotubes in rat’s lung epithelial and cervical cancer cells. J Nanosci Nanotechnol. 2015;15:2105–2114.
  • Mrakovcic M, Meindl C, Leitinger G, et al. Carboxylated short single-walled carbon nanotubes but not plain and multi-walled short carbon nanotubes show in vitro genotoxicity. Toxicol Sci Off J Soc Toxicol. 2015;144:114–127.
  • Boisselier E, Astruc D. Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem Soc Rev. 2009;38:1759–1782.
  • Lewinski N, Colvin V, Drezek R. Cytotoxicity of Nanoparticles. Small. 2008;4:26–49.
  • Bajak E, Fabbri M, Ponti J, et al. Changes in Caco-2 cells transcriptome profiles upon exposure to gold nanoparticles. Toxicol Lett. 2015;233:187–199. .
  • Walker MS, Hughes TA. Messenger RNA expression profiling using DNA microarray technology: diagnostic tool, scientific analysis or un-interpretable data? Int J Mol Med. 2008;21:13–17.
  • Jeon H, Kim J, Lee YM, et al. Poly-paclitaxel/cyclodextrin-SPION nano-assembly for magnetically guided drug delivery system. J Control Release Off J Control Release Soc. 2016;231:68–76.
  • Walther TC, Mann M. Mass spectrometry-based proteomics in cell biology. J Cell Biol. 2010;190:491–500.
  • Gioria S, Chassaigne H, Carpi D, et al. A proteomic approach to investigate AuNPs effects in Balb/3T3 cells. Toxicol Lett. 2014;228:111–126.
  • Gioria S, Vicente JL, Barboro P, et al. A combined proteomics and metabolomics approach to assess the effects of gold nanoparticles in vitro. Nanotoxicology. 2016;10:736–748.

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