Free-Blockage Mesoporous Silica Nanoparticles Loaded with Cerium Oxide as ROS-Responsive and ROS-Scavenging Nanomedicine

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 H2O2, 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 H2O2 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.

Automated summary

Mesoporous silica nanoparticles (MSNs) with a reactive oxygen species (ROS)-responsive nanogate have been extensively studied for biomedical applications. However, the current physical blockage methods used to control release are limited by their sealing ability and biocompatibility. In this study, researchers propose a design of free-blockage MSNs with methylthiopropyl units as ROS-responsive switches. By optimizing synthetic pathways, the quantity, localization, and chemical structure of the functional units, as well as the mesoporous structure of the silica, can be controlled to obtain desired products. The ROS-responsive methylthiopropyl groups can be oxidized to sulfoxides in the presence of H2O2, leading to the hydrophobic/hydrophilic conversion of the MSNs. As a proof-of-concept, ultrasmall cerium oxide nanoparticles are encapsulated into the functionalized MSNs and released within a short time period, effectively scavenging ROS. This study presents a novel design for a ROS-controlled release system, which can potentially be used in targeted drug delivery combined with antioxidant therapy.