Abstract
BACKGROUND: Stimuli-responsive drug delivery systems have been proven to be a promising strategy to enhance tumor localization, overcome multidrug resistance (MDR), and reduce the side effects of chemotherapy agents. OBJECTIVES: In this study, a temperature and redox dual stimuli-responsive system using mesoporous silica nanoparticles (MSNs) for targeted delivery of doxorubicin (DOX) was developed. METHODS: Mesoporous silica nanoparticles were capped with poly(N-isopropylacrylamide) (PNIPAM), a thermo-sensitive polymer, with atom transfer radical polymerization (ATRP) method, via disulfide bonds (DOX-MSN-S-S-PNIPAM) to attain a controlled system that releases DOX under glutathione-rich (GSH-rich) environments and temperatures above PNIPAM's lower critical solution temperature (LCST). Morphological and physicochemical properties of the nanoparticles were indicated using transmission electron microscopy (TEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Brunauer-Emmett-Teller (BET). The drug release tests were performed at 25°C and 41°C in the absence and presence of the DTT, and the obtained results confirmed the synergic effect of temperature and reductive agent on a dual responsive release profile with a 73% cumulative release at 41°C and reductive environment during 240 min. RESULTS: The average loaded drug content and encapsulation efficacy were reported as 42% and 29.5% at the drug: nanoparticle ratio of 1.5: 1. In vitro cytotoxicity assays on MCF-7 cell lines indicated significant viability decreased in cells exposed to DOX-MSN-S-S-PNIPAM compared to the free drug (DOX). CONCLUSIONS: Based on the results, DOX-MSN-S-S-PNIPAM has shown much more efficiency with stimuli-responsive properties in comparison to DOX on MCF-7 cancer cell lines.