Photoresponsive Nanovehicle for Two Independent Wavelength Light-Triggered Sequential Release of P-gp shRNA and Doxorubicin To Optimize and Enhance Synergistic Therapy of Multidrug-Resistant Cancer

Prerelease of RNA molecules than chemotherapeutic drugs with a sufficient interval is a vital prerequisite for RNA/drug co-delivery strategy to overcome multidrug resistance (MDR) of cancer cells, but how to precisely control their release at different time points is still a grand challengeup to now. This study aims to on-demand remotely manipulateRNA and drug release in real time through single delivery system to sequentially play their respective roles for optimizing and enhancing their synergistic antitumor effects. To this end, a photoresponsive mesoporous silica nanoparticle (PMSN) is fabricated as a co-delivery vehicle of P-glycoprotein(P-gp) short-hairpin RNA (shRNA) and photocaged prodrug of doxorubicin (DOX), by which the orthogonal and sequential release of shRNA and DOX can be achieved using an external light. In our design, the cationic poly[2-(N,N-dimethylaminoethyl)methacrylate] is introduced onto the PMSN surface through a light-sensitive coumarin ester derivative linker to adsorb P-gp s...