Abstract 5512: Zirconium phosphate nanoparticle matrix as potential delivery system for cisplatin to cancer cells in vitro

Abstract

Abstract Cisplatin (cis-diamminedichloroplatinum(II), have been shown to be active against ovarian and testicular cancer, Hodgkin's lymphoma, and certain other malignancies, however, its clinical effectiveness is limited by significant side effects and the emergence of drug resistance. Delivery of anticancer drugs such as cisplatin to the tumor cells without damaging healthy organs or tissues is highly difficult if not impossible. In the last several years nanoparticle-mediated drug delivery is being studied as a novel valuable mean for overcoming this problem. We developed a novel nanoparticle intercalated formulation of cisplatin on a layered matrix of zirconium phosphate (ZrP). It was expected that cisplatin, while being excluded from the external medium within ZrP layers will remain biologically inactive and that cisplatin will be released selectively in the tumor cell. The purpose of this study was to determine the cytotoxicity and effectiveness of ZrP nanoparticles in the delivery of cisplatin. Cell viability was measured by MTT assay. Flow cytometry analysis was used to determine cisplatin-induced apoptosis, and cell cycle distribution. ZrP alone did not affect the viability of breast cancer cells (MCF-7), human leukemic lymphoblast (CEM) and human peripheral blood lymphocytes (PBLs) after 24 hours in contact with different concentrations of ZrP. Cisplatin intercalated into ZrP at the highest concentration (30 μM cisplatin) reduced in 40% the cell viability of MCF-7 and CEM. The IC50 of cisplatin alone in MCF-7 was 10 μM. The side scatter plot showed that normal PBLs scatter plot is different from PBLs that have been in contact with cisplatin-intercalated ZrP for 18 hours. These PBLs carrying ZrP were displaced to the right quadrant suggesting an increased granularity that can be associated to the incorporation of ZrP nanoparticles. Moderate cisplatin-induced apoptosis was evident in cells treated with ZrP-intercalated cisplatin for 18 hours. The cell cycle analysis showed that ZrP alone does not cause cell cycle arrest. Our results suggest that application of ZrP nanoparticle-mediated drug transport in cancer chemotherapy is highly promising and more studies are warranted. 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 5512.