Noncovalent Polymer‐Gatekeeper in Mesoporous Silica Nanoparticles as a Targeted Drug Delivery Platform

Selective targeting of tumor cells and release of drug molecules inside the tumor microenvironment can reduce the adverse side effects of traditional chemotherapeutics because of the lower dosages required. This can be achieved by using stimuli-responsive targeted drug delivery systems. In the present work, a robust and simple one-pot route is developed to synthesize polymer-gatekeeper mesoporous silica nanoparticles by noncovalent capping of the pores of drug-loaded nanocontainers with disulfide cross-linkable polymers. The method offers very high loading efficiency because chemical modification of the mesoporous nanoparticles is not required; thus, the large empty pore volume of pristine mesoporous silica nanoparticles is entirely available to encapsulate drug molecules. Furthermore, the polymer shell can be easily decorated with a targeting ligand for selective delivery to specific cancer cells by subsequent addition of the thiol-containing ligand molecule. The drug molecules loaded in the nanocontainers can be released by the degradation of the polymer shell in the intracellular reducing microenvironment, which consequentially induces cell death.