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An enzyme-responsive colon-specific delivery system was developed based on hollow mesoporous silica spheres (HMSS) to which biodegradable chitosan (CS) was attached via cleavable azo bonds (HMSS–N=N–CS). Doxorubicin (DOX) was encapsulated in a noncrystalline state in the hollow cavity and mesopores of HMSS with the high loading amount of 35.2%. In vitro drug release proved that HMSS–N=N–CS/DOX performed enzyme-responsive drug release. The grafted CS could increase the biocompatibility and stability and reduce the protein adsorption on HMSS. Gastrointestinal mucosa irritation and cell cytotoxicity results indicated the good biocompatibility of HMSS and HMSS–N=N–CS. Cellular uptake results indicated that the uptake of DOX was obviously increased after HMSS–N=N–CS/DOX was preincubated with a colonic enzyme mixture. HMSS–N=N–CS/DOX incubated with colon enzymes showed increased cytotoxicity, and its IC 50  value was three times lower than that of HMSS–N=N–CS/DOX group without colon enzymes. The present work lays the foundation for subsequent research on mesoporous carriers for oral colon-specific drug delivery.

Chitosan-capped enzyme-responsive hollow mesoporous silica nanoplatforms for colon-specific drug delivery