Enhanced precision of in-vivo stable non-covalent polymergatekeepers in mesoporous silica nanoparticles for hydrophobic drug delivery in tumor therapy

Abstract

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.