(718f) 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.