enzyme and thermo dual-stimuli responsive dox carrier based on pnipam conjugated mesoporous silica

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.