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Gold nanoparticles for the improved anticancer drug delivery of the active component of oxaliplatin

Brown, Sarah D. and Nativo, Paola and Smith, Jo-Ann and Stirling, David and Edwards, Paul R. and Venugopal, Balaji and Flint, David J. and Plumb, Jane A. and Graham, Duncan and Wheate, Nial J. (2010) Gold nanoparticles for the improved anticancer drug delivery of the active component of oxaliplatin. Journal of the American Chemical Society, 132 (13). pp. 4678-4684. ISSN 0002-7863

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Abstract

The platinum-based anticancer drugs cisplatin, carboplatin, and oxaliplatin are an important component of chemotherapy but are limited by severe dose-limiting side effects and the ability of tumors to develop resistance rapidly. These drugs can be improved through the use of drug-delivery vehicles that are able to target cancers passively or actively. In this study, we have tethered the active component of the anticancer drug oxaliplatin to a gold nanoparticle for improved drug delivery. Naked gold nanoparticles were functionalized with a thiolated poly(ethylene glycol) (PEG) monolayer capped with a carboxylate group. [Pt(1R,2R-diaminocyclohexane)(H2O)2]2NO3 was added to the PEG surface to yield a supramolecular complex with 280 (±20) drug molecules per nanoparticle. The platinum-tethered nanoparticles were examined for cytotoxicity, drug uptake, and localization in the A549 lung epithelial cancer cell line and the colon cancer cell lines HCT116, HCT15, HT29, and RKO. The platinum-tethered nanoparticles demonstrated as good as, or significantly better, cytotoxicity than oxaliplatin alone in all of the cell lines and an unusual ability to penetrate the nucleus in the lung cancer cells.