Gold Nanoparticles for the Improved Anticancer Drug Delivery of the Active Component of Oxaliplatin

摘要

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