Intratumoral Delivery of TATp Bearing Paclitaxel-Loaded Micelles Demonstrates Improved in Vitro and in Vivo Cytotoxicity
R.R. Sawant, V.P. Torchilin
Northeastern University, US
Keywords: polymeric micelles, Polyethyleneglycol-phosphatidylethanolamine, cell penetrating peptide, TAT peptide, intratumoral delivery, paclitaxel
Abstract:Polyethyleneglycol-phosphatidylethanolamine (PEG-PE) micelles loaded with paclitaxel (PCT) have been prepared and the cell penetrating peptide TATp was attached to the distal tip of the PEG in PEG -PE micelles so as to allow direct contact with cells. The TATp modified micelles demonstrated increased interaction with cancer cells compared to non-modified micelles resulting in significant increase in in vitro cytotoxicity against different cancer cells. These micelle formulations along with free PCT were administered intratumorally in tumor bearing mice and induction of apoptosis was studied after 48h with the Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) assay. Free PCT and non-modified PCT-loaded micelles resulted in very few TUNEL-positive cells in tumors. The most significant amount of apoptotic cell death was observed in tumor treated with PCT-loaded micelles modified with TATp.