Xiaohui Ju

Mesoporous silica nanoparticles (MSNs) with reactive oxygen species (ROS)‐responsive “nanogate” as drug delivery platforms are extensively investigated for biomedical applications. However, the physical blockages used to control the cargo release are often limited by their poor sealing ability and low biocompatibility. Herein, a design of free‐blockage MSNs with methylthiopropyl units is proposed as the ROS‐responsive switch. Four synthetic routes are compared with different precursors through either co‐condensation or grafting methods to achieve the methylthio‐functionalized MSNs. The quantity, localization, and chemical structure of the functional units, as well as the mesoporous structure of the silica can be tuned by optimizing the synthetic pathways to obtain desired final products. The ROS‐responsive methylthiopropyl groups can be oxidized to sulfoxides in response to the presence of H 2 O 2 , leading to the hydrophobic/hydrophilic conversion of the MSNs. As a proof‐of‐concept design, ultrasmall cerium oxide nanoparticles are encapsulated into the functionalized MSNs and released out within 10 min scavenging more than 80% of the H 2 O 2 in an ROS‐rich environment. This study provides a novel design of a free‐blockage ROS‐controlled release system loaded with ROS‐scavenging nanoparticles for the future application of targeted drug delivery systems combined with antioxidant therapy.