Abstract 368: MUC1-targeted gold nanoparticle-based theranostic approach

Abstract

Abstract MUC1 is a large transmembrane glycoprotein, extending 200-400 nm from the apical surface of normal polarized epithelial cells in a variety of mucosal tissues. The large ectodomain contains a series of heavily glycosylated tandem repeats and serves as a protective barrier to enzymatic degradation and microbial attack, as well as prevents embryo attachment during the non-receptive phase in the uterus. Many cancers, including endometrial carcinomas, overexpress MUC1 which is believed to promote tumor progression by protecting tumor cells from the immune system, inhibiting apoptosis, and increasing resistance to various chemotherapeutic agents. The availability of MUC1 glycoform-specific antibodies creates an opportunity to exploit the increased or aberrant MUC1 expression in carcinoma cells by creating MUC1-targeted therapies. Gold nanoparticles (AuNPs) conjugated to a human MUC1 ectodomain specific antibody (214D4) are readily endocytosed by MUC1 expressing human endometrial cells (HES) in vitro and, following exposure to a short laser pulse, can be used to form transient vapor bubbles (plasmonic nanobubbles) capable of destroying a cell by mechanically disrupting the cell membrane. In this work, we compare the selective targeting capabilities of MUC1-targeted AuNPs using the human endometrial epithelial cell line HES and endometrial carcinoma cell lines HEC1A and HEC1B. In addition, we have used human MUC1-expressing transgenic mouse lines to examine the feasibility of using AuNP-214D4 targeting in mouse endometrium. These results demonstrate the potential use of MUC1-targetted AuNPs to detect and destroy, as well as deliver cargo, to MUC1 expressing tumors. (Supported by NIH grants HD29963 to DDC, and MD Anderson Gynecologic SPORE for Uterine Cancers 2 P50 CA098258-06 to DDC and RB). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 368. doi:10.1158/1538-7445.AM2011-368