Targeted delivery mediated by ligand modified nanocarriers have been extensively pursued for cancer chemotherapy, however the efficiency is still limited by premature drug release after the administration. Herein, we represented a simple, one-pot synthesis and robust method by installing non-covalent polymer gatekeepers in mesoporous silica nanoparticles. The unmodified mesoporous silica nanocontainers have a high loading capacity for hydrophobic drugs. This is a tumor adaptable drug carrier made of disulfide bonded polyethylene glycol-pyridyl disulfide (PEG-PDS) polymer gatekeepers and can release drug upon the increased intracellular glutathione concentration. In-situ covalently crosslinked the PEG-PDS capped mesoporous silica nanoparticles have shown improved encapsulation to avoid the premature drug release. Intravenously injected non-covalent polymergatekeepers have led to hydrophobic doxorubicin in cancer cells and suppresses the tumor growth in mice. As compared to the self-assembled micelles, doxorubicin loaded polymergatekeeper mesoporous nanoparticles have shown improved tumor reducing capability.