Evaluation of the Toxicity of Intravenous Delivery of Auroshell Particles (Gold-Silica Nanoshells)
Evaluation of the Toxicity of Intravenous Delivery of Auroshell Particles (Gold-Silica Nanoshells)
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Auroshell 颗粒（金-二氧化硅纳米壳）静脉给药的毒性评价
DOI：
10.1177/1091581812465969
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发表时间：
2012-11-01
影响因子：
2.2
通讯作者：
Goodrich, Glenn P.
中科院分区：
文献类型：
--
作者：
Gad, Shayne C.;Sharp, Kelly L.;Goodrich, Glenn P.
评价金纳米壳（直径155 nm，具有聚乙二醇5000涂层）的临床前生物相容性、毒性和生物分布，作为开发用于肿瘤光热消融的可注射器械的计划的一部分。评价开始于符合国际标准化组织（ISO）-10993生物相容性计划的完整药物非临床研究质量管理规范（GLP），包括细胞毒性、热原性（美国药典[USP]家兔方法），遗传毒性（细菌致突变性、中国仓鼠卵巢细胞染色体畸变试验和体内小鼠微核试验）、体外溶血、家兔皮内反应性，致敏性（豚鼠最大剂量致敏试验）和USP/ISO小鼠急性全身毒性。所有研究均未发现毒性迹象。随后，在小鼠、Sprague-Dawley大鼠和比格犬的一系列研究中，通过静脉（iv）输注使用海藻糖/水溶液在体内评价纳米壳，以评估长达404天的毒性。在14项GLP研究过程中，金纳米壳耐受性良好，静脉注射时，未发现毒性或生物不相容性。
Gold nanoshells (155 nm in diameter with a coating of polyethylene glycol 5000) were evaluated for preclinical biocompatibility, toxicity, and biodistribution as part of a program to develop an injectable device for use in the photothermal ablation of tumors. The evaluation started with a complete good laboratory practice (GLP) compliant International Organization for Standardization (ISO)-10993 biocompatibility program, including cytotoxicity, pyrogenicity (US Pharmacopeia [USP] method in the rabbit), genotoxicity (bacterial mutagenicity, chromosomal aberration assay in Chinese hamster ovary cells, and in vivo mouse micronucleus), in vitro hemolysis, intracutaneous reactivity in the rabbit, sensitization (in the guinea pig maximization assay), and USP/ISO acute systemic toxicity in the mouse. There was no indication of toxicity in any of the studies. Subsequently, nanoshells were evaluated in vivo by intravenous (iv) infusion using a trehalose/water solution in a series of studies in mice, Sprague-Dawley rats, and Beagle dogs to assess toxicity for time durations of up to 404 days. Over the course of 14 GLP studies, the gold nanoshells were well tolerated and, when injected iv, no toxicities or bioincompatibilities were identified.