Size-dependent localization and penetration of ultrasmall gold nanoparticles in cancer cells, multicellular spheroids, and tumors in vivo.
Size-dependent localization and penetration of ultrasmall gold nanoparticles in cancer cells, multicellular spheroids, and tumors in vivo.
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DOI：
10.1021/nn301282m
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发表时间：
2012-05-22
期刊：
影响因子：
17.1
通讯作者：
Liang XJ
中科院分区：
文献类型：
--
作者：
Huang K;Ma H;Liu J;Huo S;Kumar A;Wei T;Zhang X;Jin S;Gan Y;Wang PC;He S;Zhang X;Liang XJ
这项工作表明，小于10 nm的超小金纳米颗粒（AuNPs）在定位和渗透乳腺癌细胞、多细胞肿瘤球体和小鼠肿瘤方面显示出比大于10 nm的纳米颗粒独特的优势。成功地制备了Au@硫普罗宁纳米颗粒，其具有从2至15 nm的可调尺寸，具有相同的硫普罗宁表面涂层和电荷。对于单层细胞，Au@硫普罗宁NPs越小，在每个细胞中发现的AuNPs越多。此外，Au NPs在离体肿瘤模型中的积累是尺寸依赖性的：较小的AuNPs能够深入渗透到肿瘤球状体中，而15 nm的纳米颗粒则不能。由于其超小的纳米结构，2和6 nm纳米颗粒在单次静脉注射后在小鼠肿瘤组织中显示出高水平的积累。令人惊讶的是，2和6 nm Au@硫普罗宁纳米颗粒在体外和体内分布在癌细胞的整个细胞质和细胞核中，而15 nm Au@硫普罗宁纳米颗粒仅在细胞质中发现，在那里它们形成聚集体。离体多细胞球体被证明是模拟体内肿瘤组织和评估纳米颗粒渗透行为的良好模型。这项工作为纳米颗粒的设计和功能化提供了重要的见解，以实现肿瘤中的高水平积累。
This work demonstrated that ultrasmall gold nanoparticles (AuNPs) smaller than 10 nm display unique advantages over nanoparticles larger than 10 nm in terms of localization to, and penetration of, breast cancer cells, multicellular tumor spheroids, and tumors in mice. Au@tiopronin nanoparticles that have tunable sizes from 2 to 15 nm with identical surface coatings of tiopronin and charge were successfully prepared. For monolayer cells, the smaller the Au@tiopronin NPs, the more AuNPs found in each cell. In addition, the accumulation of Au NPs in the ex vivo tumor model was size-dependent: smaller AuNPs were able to penetrate deeply into tumor spheroids, whereas 15 nm nanoparticles were not. Owing to their ultrasmall nanostructure, 2 and 6 nm nanoparticles showed high levels of accumulation in tumor tissue in mice after a single intravenous injection. Surprisingly, both 2 and 6 nm Au@tiopronin nanoparticles were distributed throughout the cytoplasm and nucleus of cancer cells in vitro and in vivo, whereas 15 nm Au@tiopronin nanoparticles were found only in the cytoplasm, where they formed aggregates. The ex vivo multicellular spheroid proved to be a good model to simulate in vivo tumor tissue and evaluate nanoparticle penetration behavior. This work gives important insights into the design and functionalization of nanoparticles to achieve high levels of accumulation in tumors.
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影响因子：
7.3
作者：
Goldsborough AS;Handley MD;Dulcey AE;Pluchino KM;Kannan P;Brimacombe KR;Hall MD;Griffiths G;Gottesman MM
通讯作者：
Gottesman MM
影响因子：
38.3
作者：
Jiang, Wen;Kim, Betty Y. S.;Chan, Warren C. W.
通讯作者：
Chan, Warren C. W.
DOI：
10.1016/j.jconrel.2010.06.004
发表时间：
2010-11-20
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Duncan B;Kim C;Rotello VM
通讯作者：
Rotello VM
影响因子：
38.3
作者：
通讯作者：
--
影响因子：
17.1
作者：
Massich, Matthew D.;Giljohann, David A.;Mirkin, Chad A.
通讯作者：
Mirkin, Chad A.