Design and characterization of dual responsive mesoporous silica nanoparticles for breast cancer targeted therapy

Abstract

The main reason for limited efficacy of anticancer drug is the poor accretion of administered amount of drug within the tumor. Here, chitosan folate capped dual responsive mesoporous silica nanoparticles (MSNs) which can actively target cancer cells, and provide burst release of loaded anticancer drug within tumor cells and ultimately leading to improved therapeutic efficacy were synthesized. MSNs were synthesized using most economic silica source, sodium silicate. Doxorubicin (DOX) was loaded within the pores of MSNs and these drug loaded MSNs were first reacted with cystamine dihydrochloride followed by capping with chitosan-folate conjugate (CH-FA) to produce dual (redox and pH) responsive nanoparticles with the ability to actively target breast cancer cells. A triggered release of DOX from MSNs under acidic redox (pH 5.5, 10 mM GSH) environment was confirmed by in vitro release studies. The formulation exhibited 2.14 and 1.65 folds higher cytotoxicity than free drug against MCF-7 and MDA-MB-231 cells. DOX-MSN-SS-CH-FA showed superior tumor suppressing activity as compared to DOX-MSN or DOX alone in the treatment of Ehrlich Ascites Carcinoma (EAC) induced breast cancer with significantly reduced hematological and organ specific toxicities associated with DOX treatment.