SILK FIBROIN BASED NANOCARRIERS FOR DELIVERY OF ANTIOXIDANT AND IMAGING AGENT

Abstract

Silk fibroin is an abundantly available biopolymer which has versatile properties such as biocompatibility, biodegradability, and pH dependent drug release. All of these properties make silk as a potential candidate for biological applications such as wound healing, scaffolds for tissue engineering and suture materials etc [1]. The present study deals with exploring the potential of silk fibroin as a carrier for antioxidant and imaging agents for the removal of harmful reactive oxygen species (ROS) for the treatment of oxidative stress related disorders. Silk fibroin was initially isolated from mulberry bombyx mori silk cocoons using degumming method. Then single step desolvation method was used to prepare sulforaphane drug loaded silk fibroin nanoparticles (SFSNPs). In order to enhance their potential as an anti-oxidant theranostic agent, these synthesised drug loaded nanoparticles were further coupled with cerium oxide nanoparticles (CeNPs) and carbon dots (CDs). The presence CDs in the nanocomposites facilitated cellular imaging and cellular uptake while CeNP augmented their antioxidant potential The overall composite is known as self-assembled CeNP-CD@SFSNPs fluorescent nano composites. CeNPs were synthesised using a single step hydrothermal method. CDs were also synthesized using mulberry leaves as a source via hydrothermal method. The coupling of CDs and CeNPs with SFSNPs involved electrostatic interactions between negatively charged drug loaded silk fibroin nanoparticles and positively charged CeNPs and CDs which was confirmed by reduction of zeta potential of SFSNPs from 32 mV to 15 mV. These synthesized SFSNPs and fluorescent nanocomposites were characterized using various advanced analytical techniques such as DLS, Zeta potential, FE-SEM, XRD, FTIR, HR-TEM, UV-Vis Spectroscopy, fluorescence spectroscopy and TGA/DTA. Time dependent in vitro drug release was carried out in two different pH environments. The in vitro studies such cytotoxicity, cellular uptake, cellular

imaging and ROS analysis were also performed on MCF-7 breast cancer cell lines to analyze the cytotoxicity and antioxidant behavior of these composites. Moreover, SOD (superoxide dismutase) activity was also checked using SOD kit. The development of such anti-oxidant mimetic theranostic system using silk fibroin have an immense potential in treatment of oxidative stress related disorders.