Size-Dependent Localization and Penetration of Ultrasmall Gold Nanoparticles in Cancer Cells, Multicellular Spheroids, and Tumors in Vivo

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...

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Bibliographic Details
Published in:ACS nano 2012-05, Vol.6 (5), p.4483-4493
Main Authors: Huang, Keyang, Ma, Huili, Liu, Juan, Huo, Shuaidong, Kumar, Anil, Wei, Tuo, Zhang, Xu, Jin, Shubin, Gan, Yaling, Wang, Paul C, He, Shengtai, Zhang, Xiaoning, Liang, Xing-Jie
Format: Article
Language:English
Subjects:
Biomedical materials
Cancer
Cell Line, Tumor
Gold
Gold - chemistry
Humans
In vivo tests
Metal Nanoparticles
Nanoparticles
Neoplasms - pathology
Penetration
Spheroids
Surgical implants
Tumors
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Summary: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.
ISSN:1936-0851
1936-086X
DOI:10.1021/nn301282m