Abstract 4523: Targeted delivery to tumor cells by using tunable nano-delivery system with chlorotoxin.
Authors: Falahat Rana , Williams Eva Christabel , Wiranowska Marzenna , Toomey Ryan , Alcantar Norma 
Published: August 2014

The aim of this research is to develop the Tunable Nano-Delivery System (TNDS) for specific targeting of the tumor cells using Chlorotoxin (CTX). We present preliminary findings for the TNDS localized drug delivery system comprising of non-ionic surfactant vesicles (niosomes) with CTX embedded in a biodegradable and temperature sensitive chitosan network. The system demonstrates a new approach in the treatment of cancers, through the controlled and targeted delivery to tumor cells (the release time and dosage can be accurately controlled) while sparing normal cells. CTX is a scorpion-derived peptide that binds specifically to neuroectodermal tumors, e.g., glioma, but not to normal tissues. Previously, we have shown that there is a specific interaction between chitosan and Mucin1 (MUC1) receptors over expressed in epithelial ovarian carcinoma resulting in higher chitosan accumulation on the cancer cell surface than on normal ovarian epithelial cells.

The current research addresses the incorporation of CTX embedded in Chitosan network to enhance specific targeting, which already benefits from the intrinsic interaction of MUC1 with Chitosan. Our current studies incorporating CTX in chitsoan resulting in TNDS-CTX complex are preformed in cell-free system. First, the release rates and release kinetics of TNDS-CTX are being measured in cell-free system using High Performance Liquid Chromatography (HPLC) and Attenuated Total Reflectance- Fourier Transform Infra-Red (ATR-FTIR) spectroscopy. Results are being compared to our established TNDS delivery system to better determine CTX specific chemical binding sites along with the sites already determined to be specific for MUC1. Next, we will be testing TNDS-CTX in vitro in glioma, epithelial ovarian carcinoma, and normal ovarian epithelial and astrocyte cells. The level of fluorescence of normal cells and tumor cells exposed to the TNDS-CTX-fluorescently labeled are evaluated in in vitro by confocal microscopy. The studies in cell-free system showed that the release rates could be finely controlled depending on the specific design of the TNDS-CTX e.g., ratio of niosomes to chitosan and amount of crosslinker for the chitosan network.

We are currently evaluating TNDS-CTX containing benchmark chemotherapeutics such as Paclitaxel, and it is expected that the presence of CTX will enhance cellular uptake of chemotherapeutics when compared to the noisome-chitosan delivery system without CTX. Based on our preliminary data, it is anticipated that CTX will perform as a targeting ligand improving the TNDS-CTX's anti-tumor efficacy owing to enhanced tumor targeting and its tunable and localized delivery.

Citation Format: Rana Falahat, Eva Christabel Williams, Marzenna Wiranowska, Ryan Toomey, Norma Alcantar. Targeted delivery to tumor cells by using tunable nano-delivery system with chlorotoxin. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4523. doi:10.1158/1538-7445.AM2013-4523