Abstract 3516: Targeting cancer by cisplatin-containing nanovectors

Abstract

Abstract Cisplatin [cis-dichlorodiammineplatinum(II)] is a first-line chemotherapeutic agent, and is widely used for the treatment of many malignancies including testicular, ovarian, cervical, head and neck, and non-small cell lung cancer. Its use is dose-limited mainly because of nephrotoxicity. To address this limitation, we have engineered novel nanovector to deliver the drug directly to the tumor site with reduced toxicity. In this study, we have functionalized cholesterol with succinic acid and ethyelene diammine to complex platinum through a monocarboxylato and a coordinate bond. The Chol-Pt complex was mixed with phosphatidylcholine and DSPE-PEG at 5:10:1 weight ratio and cisplatin containing nanoparticles were synthesized through evaporation-hydration-extrusion technique. The nanoparticles were found to be in the size range of 100-150 nm and spherical in morphology (characterized by DLS and TEM respectively). The physicochemical release kinetics of cisplatin from the nanoparticles in different hypoxic cell lysates showed a sustained release of the drug. Our in vitro studies of the cisplatin liposomes indicate that cisplatin liposomes are highly effective in 4T1 breast cancer and LLC (Lewis Lung Carcinoma) cell lines in 48 hours, as compared with free cisplatin. Most interestingly, our cisplatin containing liposomes demonstrated efficacy in cisplatin resistant CP20 (liver adenocarcinoma) cell line at 10 μM concentration. Hence, our study showed that our novel cisplatin nanovector delivery device could potentially be harnessed for lung, breast and cisplatin resistant cancer chemotherapy with increased therapeutic index compared to cisplatin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3516.