Size-Dependent Localization and Penetration of Ultrasmall Gold Nanoparticles in Cancer Cells, Multicellular Spheroids, and Tumors in Vivo
By Keyang Huang, Huili Ma, Juan Liu, Shuaidong Huo, Ajay Kumar, Tuo Wei, Xu Zhang, Shubin Jin, Yaling Gan, Paul C. Wang and 3 more. ACS Nano, 2012
800 citations recorded by the source corpus.
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.
View Paper: https://www.semanticscholar.org/paper/607a3b092f111622d3fd36a05ecc118a845f5df6
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Citations in the corpus
- Engineered nanoparticles interacting with cells: size matters (2014, unknown): “Au 2–15 MCF-7 ICP-MS, TEM Higher uptake of smaller NPs; 2/6 nm locate in cytoplasm and nucleus, 15 nm only in cytoplasm [44]”
- Gold nanoparticle-mediated photothermal therapy: applications and opportunities for multimodal cancer treatment (2017, background): “Notably, the size and shape of AuNPs also influence their ability to extravasate from vasculature and penetrate solid tumors, which will ultimately impact the success of PTT because it will influence how evenly heat is distributed throughout the tumor.(25,26) For example, Perrault et al.”