In Vitro and in Vivo Approach of Hydrogen-Sulfide-Responsive Drug Release Driven by Azide-Functionalized Mesoporous Silica Nanoparticles

Cancer has become a major cause of human death in many countries. Generally, chemotherapy is the main treatment for cancer, but it may kill both cancerous cells as well as normal cells that cause serious side effects in the patient due to lack of specific targeting for cancerous cells. In order to achieve better efficiency in the cancer treatment, the development of targeted drug delivery platform has been a goal for a long time. Herein, we constructed folic acid decorated azide functionalized biocompatible mesoporous silica nanoparticles (MSNPs) to target tumor cells through folate receptor (FR), a widely expressed receptor in cancer cells. In colon and ovarian cancer cells, high endogenous H₂S levels are found. They can be used as a trigger for the azide reduction, which leads to the cleavage of ester linkage and results in DOX release from MSNP nanocarriers. Additionally, confocal cell images of HCT-116, HT-29, A2780, SKOV3, and HeLa cells treated with nanoparticles revealed an effective internalization of MSNPs in these cells. Interestingly, DOX-loaded MSNP-N₃-FA-treated HT-29 cells showed a significant decrease in the cell viability, whereas, there was no substantial change in HeLa cells. We also demonstrated that DOX-loaded MSNP-N₃-FA has superior in vivo chemotherapy efficacy compared to free DOX. These observations indicated that the designed nanocarriers on MSNP-N₃-FA specifically respond in the presence of H₂S. MSNP-N₃-FA is the first potential nanocarrier for endogenous H₂S-based efficient DOX release for colon and ovarian cancers.