title: Surface chemistry but not aspect ratio mediates the biological toxicity of gold nanorods in vitro and in vivo.
abstract: Gold nanorods are a promising nanoscale material in clinical diagnosis and treatment. The physicochemical properties of GNRs, including size, shape and surface features, are crucial factors affecting their cytotoxicity. In this study, we investigated the effects of different aspect ratios and surface modifications on the cytotoxicity and cellular uptake of GNRs in cultured cells and in mice. The results indicated that the surface chemistry but not the aspect ratio of GNRs mediates their biological toxicity. CTAB-GNRs with various aspect ratios had similar abilities to induce cell apoptosis and autophagy by damaging mitochondria and activating intracellular reactive oxygen species (ROS). However, GNRs coated with CTAB/PSS, CTAB/PAH, CTAB/PSS/PAH or CTAB/PAH/PSS displayed low toxicity and did not induce cell death. CTAB/PAH-coated GNRs caused minimally abnormal cell morphology compared with CTAB/PSS and CTAB/PSS/PAH coated GNRs. Moreover, the intravenous injection of CTAB/PAH GNRs enabled the GNRs to reach tumor tissues through blood circulation in animals and remained stable, with a longer half-life compared to the other GNRs. Therefore, our results demonstrated that further coating can prevent cytotoxicity and cell death upon CTAB-coated GNR administration, similar to changing the GNR aspect ratio and CTAB/PAH coated GNRs show superior biological properties with better biocompatibility and minimal cytotoxicity.
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, P R China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Wan
authors.affiliation: Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China.
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, P R China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, P R China.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, CAS Key Lab of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Yu
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, P R China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000494:pharmacology*; D006046:Gold / Q000633:toxicity*; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects; D043942:Nanotubes / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D013499:Surface Properties; D013501:Surface-Active Agents / Q000494:pharmacology*
chemical_list: D002593:Cetrimonium Compounds; D017382:Reactive Oxygen Species; D013501:Surface-Active Agents; D006046:Gold; D000077286:Cetrimonium