title: Nanotoxicology: advances and pitfalls in research methodology.
abstract: As research progresses, nanoparticles (NPs) are becoming increasingly promising tools for medical diagnostics and therapeutics. Despite this rise, their potential risks to human health, together with environmental issues, has led to increasing concerns regarding their use. As such, a comprehensive understanding of the interactions that occur at the nano-bio interface is required in order to design safe, reliable and efficient NPs for biomedical applications. To this end, extensive studies have been dedicated to probing the factors that define various properties of the nano-bio interface. However, the literature remains unclear and contains conflicting reports on cytotoxicity and biological fates, even for seemingly identical NPs. This uncertainty reveals that we frequently fail to identify and control relevant parameters that unambiguously and reproducibly determine the toxicity of nanoparticles, both in vitro and in vivo. An effective understanding of the toxicological impact of NPs requires the consideration of relevant factors, including the temperature of the target tissue, plasma gradient, cell shape, interfacial effects and personalized protein corona. In this review, we discuss the factors that play a critical role in nano-bio interface processes and nanotoxicity. A proper combinatorial assessment of these factors substantially changes our insight into the cytotoxicity, distribution and biological fate of NPs.
authors.affiliation: Nanotechnology Research Center & Department of Pharmacology & Toxicology Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Azhdarzadeh
authors.affiliation: Nanotechnology Research Center & Department of Pharmacology & Toxicology Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Department of Medical Biochemistry & Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Amir Ata
authors.initials: AA
authors.lastname: Saei
authors.affiliation: Department of Biomaterials Science & Technology, University of Twente, The Netherlands.
authors.forename: Shahriar
authors.initials: S
authors.lastname: Sharifi
authors.affiliation: Department of Medical Biotechnology, National Institute of Genetic Engineering & Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Mohammad J
authors.initials: MJ
authors.lastname: Hajipour
authors.affiliation: Department of Pharmaceutics & Pharmaceutical Technology, Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan.
authors.forename: Alaaldin M
authors.initials: AM
authors.lastname: Alkilany
authors.affiliation: Nanotechnology Research Center & Department of Pharmacology & Toxicology Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sharifzadeh
authors.affiliation: Faculty of Medicine & Dentistry, University of Alberta, 116 St & 85 Ave, T6G 2R3, Edmonton, Canada.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Ramazani
authors.affiliation: Department of General, Organic & Biomedical Chemistry, NMR & Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, B-7000 Mons, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Laurent
authors.affiliation: Harvard Medical School, Harvard University, 25 Shattuck St, Boston, MA 02115, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Mashaghi
authors.affiliation: Nanotechnology Research Center & Department of Pharmacology & Toxicology Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Division of Cardiovascular Medicine, School of Medicine, Stanford University, Stanford, CA, USA.|Cardiovascular Institute, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Morteza
authors.initials: M
authors.lastname: Mahmoudi
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D006801:Humans; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity*; D000066970:Protein Corona / Q000737:chemistry / Q000378:metabolism; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000066970:Protein Corona
keywords: cellular uptake; nanomedicine; nanoparticles; nanotoxicology; nano–bio interface; organ-on-a-chip; preanalytical factors; toxicity