A versatile one‐pot strategy for the preparation of reversibly cross‐linked polymer‐coated mesoporous silica nanoparticles (MSNs) via surface reversible addition–fragmentation chain transfer (RAFT) polymerization is presented for the first time in this paper. The less reactive monomer oligo(ethylene glycol) acrylate (OEGA) and the more reactive cross‐linker N,N′‐cystaminebismethacrylamide (CBMA) are chosen to be copolymerized on the external surfaces of RAFT agent‐functionalized MSNs to form the cross‐linked polymer shells. Owing to the reversible cleavage and restoration of disulfide bonds via reduction/oxidation reactions, the polymer shells can control the on/off switching of the nanopores and regulate the drug loading and release. The redox‐responsive release of doxorubicin (DOX) from this drug carrier is realized. The protein adsorption, in vitro cytotoxicity assays, and endocytosis studies demonstrate that this biocompatible vehicle is a potential candidate for delivering drugs. It is expected that this versatile grafting strategy may help fabricate satisfying MSN‐based drug delivery systems for clinical application.
