title: Genotoxicity of different nanocarriers: possible modifications for the delivery of nucleic acids.
abstract: The prevention of cyto- and genotoxicity of nanocarriers is an important task in nanomedicine. In the present investigation, we, at the first time using similar experimental conditions, compared genotoxicity of nanocarriers with different composition, architecture, size, molecular weight and charge. Poly(ethylene glycol) polymers, neutral and cationic liposomes, micelles, poly(amindo amine) and poly(propyleneimine) dendrimers, quantum dots, mesoporous silica, and supermagnetic iron oxide (SPIO) nanoparticles were studied. All nanoparticles were used in non-cytotoxic concentrations. However, even in these concentrations, positively charged cationic liposomes, dendrimers, and SPIO nanoparticles induced genotoxicity leading to the significant formation of micronuclei in cells. Negatively charged and neutral nanocarriers were not genotoxic. A strong positive correlation was found between the number of formed micronuclei and the positive charge of nanocarriers. We proposed modifications of both types of dendrimers and SPIO nanoparticles that substantially decreased their genotoxicity and allowed for an efficient intracellular delivery of nucleic acids.
authors.affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
authors.forename: Vatsal
authors.initials: V
authors.lastname: Shah
authors.forename: Oleh
authors.initials: O
authors.lastname: Taratula
authors.forename: Olga B
authors.initials: OB
authors.lastname: Garbuzenko
authors.forename: Mahesh L
authors.initials: ML
authors.lastname: Patil
authors.forename: Ronak
authors.initials: R
authors.lastname: Savla
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Tamara
authors.initials: T
authors.lastname: Minko
mesh_terms: D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D050091:Dendrimers / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity*; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000633:toxicity; D011126:Polypropylenes / Q000633:toxicity; D034741:RNA, Small Interfering / Q000008:administration & dosage; D012822:Silicon Dioxide / Q000633:toxicity
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D011126:Polypropylenes; D034741:RNA, Small Interfering; C443641:poly(propyleneimine); D011092:Polyethylene Glycols; D012822:Silicon Dioxide