Acidity and Glutathione Dual‐Responsive Polydopamine‐Coated Organic‐Inorganic Hybrid Hollow Mesoporous Silica Nanoparticles for Controlled Drug Delivery

Controversial biodegradability and nonspecific pre‐drug leakage are major limitations for inorganic nanoparticles in cancer treatment. To solve these problems, we developed organic‐inorganic hybridized hollow mesoporous silica nanoparticles with polydopamine modifications on the surface to simultaneously achieve enhanced biodegradability and controllable drug release. The morphology and chemical structure of the nanoparticles were characterized by TEM, N2 adsorption‐desorption isotherms, TEM‐mapping and XPS. Moreover, the release behavior of nanoparticles under various pH conditions and the degradation behavior in the presence of GSH were evaluated. With effective controlled release, HMONs‐PTX@PDA were shown to significantly inhibit cancer cell proliferation and achieve antitumor effects in vivo through dual‐response release in the tumor microenvironment. Overall, this nanoplatform has significant potential to achieve tumor microenvironment‐responsive degradation and release to enhance tumor accumulation, which is very promising for cancer treatment. Responsive and effective: We developed organic‐inorganic hybridized hollow mesoporous silica nanoparticles. The pH‐sensitive PDA film acted as a gatekeeper and responded to the weakly acidic environment of the tumor site. The disulfide bond was incorporated into the silica framework to rapidly biodegrade in the reducing tumor microenvironment.