pH and charge reversal-driven nanoplatform for efficient delivery of therapeutics

Nanomedicine which delivers therapeutics to tumours holds great potential for cancer treatment. However, endosomal trapping and uncontrollable release usually limit the efficiency of nanomedicine. Herein, a smart mesoporous silica based nanoplatform was constructed, in which mesoporous silica nanoparticles (MSNs) serve as the core, capped with pH-induced charge-reversal polymer -PAH-cit- and cationic polyelectrolyte polyethyleneimine (PEI). The oppositely charged polymer can not only act as a gatekeeper for controlled release, but also mediated efficient endosomal escape of the therapeutics. Under the acidic endosomal environment, the hydrolysis of acid-cleavable bonds in PAH-Cit would trigger the charge reversal and endosomal escape of the nanoplatform for efficient drug release. Furthermore, the prepared nanoplatform demonstrated a higher tumor cell proliferation inhibition rate than free theruputics in vitro assays and significantly inhibited tumour growth in the 4T1 tumour model in mice. Therefore, our strategy offers a simple and general nanoplatform to delivery therapeutics to tumours with efficient endosomal escape and controlled release.