Dual pH- and temperature-responsive poly(dimethylaminoethyl methacrylate)-coated mesoporous silica nanoparticles as a smart drug delivery system

Abstract

A robust drug delivery system was created by grafting poly(dimethylaminoethyl methacrylate) (PDMAEMA) onto silica nanoparticles with two different lengths using an in situ atom transfer radical polymerization, resulting in the formation of a pH- and temperature-sensitive shell. The high molecular weight PDMAEMA demonstrated effective controlled drug release, and prevented drug release in healthy cells. Drug release occurred through polymer shell protonation at pH 5. The critical temperature of 41 °C facilitated rapid solvation of the shell polymers in the blood, preventing tissue accumulation and reducing toxicity compared to systems with lower critical solution temperatures. Field-emission scanning electron microscopy analysis and nitrogen adsorption/desorption analysis showed that the nanoparticles have a fine network, mesoporous structure, and a mean size of around 17 nm that show their excellent capacity for loading drugs. Fourier-transform infrared spectroscopy showed that all the modification steps and polymerization were successfully implemented. Thermogravimetric analysis showed PDMAEMA chains with two different lengths grafted onto the nanoparticles. Transmission electron microscopy analysis also showed grafted polymer chains on the hybrid nanoparticles. The release profile of model cancer drugs (doxorubicin and methotrexate) varied with pH and temperature, with high molecular weight PDMAEMA shells effectively preventing drug release at neutral pH. In vitro analysis using the HeLa cell line showed minimal toxicity in blank samples and significant release profile in acidic environment.