Abstract

With the onset of hyperthermia and their advantage in increasing vascular perfusion and permeability in the cancer milieu, thermo-responsive polymers have become an attractive candidate for designing therapeutic nano-vehicles for targeted on-demand delivery of bioactive agents. For this purpose, we developed a dual (thermo- and pH-) responsive nanotherapeutic composite system rendering a combinational therapy of hyperthermia mediated drug delivery. This composite system comprises of magnetic chitosan-g-PNVCL (MCP) polymeric nanogels loaded with anticancer drug, Doxorubicin (DOX). The size distribution and the stability of the MCP nanogels have been characterized using DLS and Zeta-potential studies. XRD and TG-DTA confirms the presence of magnetic nanoparticles loaded onto MCP nanogel. ICP-AES analysis was done to determine the amount of iron content in the MCP nanogels. The magnetic property of the MCP nanogels was estimated to be ∼37 emu/g using Vibrating Sample Magnetometer (VSM). The heating ability of MCP nanogels was calculated to be ∼204W/g for the concentration of 2mg/mL using time-dependent Specific Absorption Rate (SAR) method. Magnetic field induced thermo-responsive and pH responsive drug release studies were carried out and it was found that MCP nanogels have a good on-demand drug release properties. The DOX-MCP nanogels were evaluated for its in vitro killing efficacy of breast cancer cells MCF 7 and MDAMB 231 cells with synergistic effects of both hyperthermia and chemotherapy in presence of magnetic field at the concentration of 2mg/mL. Thus, MCP nanogels can be a potential dual modal on-demand hyperthermia mediated drug delivery platform for the breast cancer treatment.

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