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

TLDR

Platinum‑based chemotherapeutics such as cisplatin, carboplatin, and oxaliplatin are effective but limited by severe dose‑limiting side effects and rapid tumor resistance. The study aims to enhance oxaliplatin efficacy by employing drug‑delivery vehicles that can target tumors passively or actively. The authors tethered oxaliplatin’s active component to gold nanoparticles functionalized with a PEG‑carboxylate monolayer, creating a supramolecular complex containing ~280 drug molecules per particle, and evaluated its cytotoxicity, uptake, and subcellular localization in lung and colon cancer cell lines. The platinum‑tethered nanoparticles exhibited cytotoxicity equal to or superior to oxaliplatin alone across all tested cell lines and uniquely penetrated the nucleus in lung cancer cells.

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.