Tunable Nano-Delivery System for Cancer Treatment With Chlorotoxin: A New Approach for Targeted Drug Delivery

Tunable Nano-Delivery System for cancer treatment with Chlorotoxin: A new approach for targeted drug delivery

 

Rana Falahat¹, Eva Williams¹, Marzenna Wiranowska², Ryan Toomey¹, Norma Alcantar¹

¹Chemical & Biomedical Engineering Department, College of Engineering,

²Department of Pathology and Cell Biology, Morsani College of Medicine,

University of South Florida

Tampa, FL-33620

 

 

We have developed a Tunable Nano-Delivery System (TNDS) using Chlorotoxin (CTX) for specific targeting of tumor cells. The TNDS consists of non-ionic surfactant vesicles (niosomes) and CTX embedded in a biodegradable and thermo-responsive chitosan hydrogel network. This system shows a new approach in the treatment of cancers, through controlled and targeted delivery to tumor cells which allows accurately controlling the release time and dosage. CTX is a 36 amino acid peptide purified from Leiurus quinquestriatus scorpion venom which binds preferentially to tumor cells but does not bind to normal tissues. Initially, the release rates and release kinetics of TNDS-CTX have been measured in cell-free system using High Performance Liquid Chromatography (HPLC) and Attenuated Total Reflectance- Fourier Transform Infra-Red (ATR-FTIR) spectroscopy. Results were compared to the drug delivery system without CTX in order to better determine CTX chemical binding sites. The topography of the TNDS-CTX system was observed using transmission electron microscopy (TEM). Results also include measuring the level of drug uptake of normal cells versus tumor cells exposed to TNDS with a fluorescently labeled drug by in vitro testing using confocal microscopy.  Our data shows that embedding CTX along with the niosomes does not disturb the controlled release from the chitosan network. In fact, CTX increases the stability of niosomes due to its attachment to the surface of niosomes resulting in slower and prolonged release rates. Based on these results, we anticipate that the TNDS with CTX as the targeting ligand would improve tumor uptake due to the enhanced tumor targeting and its controlled, sustained and localized drug delivery to cancer cells.