Rahmat Asfiya
Indian Institute of Science, Dept. Of Organic Chemistry, Bangalore, INDIA
Title: Efficacious anticancer drug delivery mediated by a short biocompatible peptide sequence targeted for colon cancer
Biography
Biography: Rahmat Asfiya
Abstract
A tetrapeptide and octapeptide sequence were synthesized to evaluate their efficiency towards the delivery of a common anticancer drug, doxorubicin. Initially we investigated the self-organization pattern of both of the peptide sequences where they exhibited concentration dependent self-assembling behaviour. Particularly the tetrapeptide showed vesicular morphology at low concentration and fibrous morphology at high concentration. The observations were corroborated from both the atomic force and transmission electron microscopic analysis.
Importantly, the self-assembled nanostructures were quite sensitive towards the pH of the medium. The vesicles, made up of either the tetra or octapeptide sequences, were stable at lower pH (~pH 5) of the medium, but ruptured rapidly at physiological pH (~pH 7.4). This pH-sensitive nature of the vesicles was then tested for the delivery of one of the widely used anticancer drug, doxorubicin (DOX), where the octapeptide showed its proficiency not only towards the encapsulation but also towards the sustained release of DOX. The drug release profile followed the pattern of pH 7.4 > pH 6 > pH 5.
The vesicles were further coated with derivatives of polyethylene glycol based lipids to increase the blood circulation time and serum stability of the DOX loaded nanoparticles. The in vitro efficacy of the system was monitored in stomach cancer cell line, AGS, and colon carcinoma cell line, CT26. The cellular internalization of DOX was found to be better when the drug was delivered by the PEGylated octapeptide system as compared to the tetrapeptide system and drug alone. The observation was confirmed from the flow cytometric, fluorescence and confocal microscopic analyses.