Mesoporous silica nanoparticle-based cisplatin prodrug delivery and anticancer effect under reductive cellular environment

Abstract

This work demonstrates the judicious application of a prodrug delivery strategy to achieve a highly improved anticancer drug e!ect of cisplatin using mesoporous silica nanoparticles. Our e!ort primarily addressed several pressing needs to overcome various impediments such as toxicity concerns, rapid inactivation, and low drug e"ciency of cisplatin prodrug. The developed delivery system utilizes #uorescent mesoporous silica nanoparticles as a template to host the cisplatin prodrug through a reducible linkage. The inactive oxidized Pt(IV) complex installed on the surface of the mesoporous silica nanoparticles in the prodrug conferred stability to cisplatin; however, in the reductive environment of cancer cell lines the active cisplatin form was regenerated. Prodrug-conjugated nanoparticles showed 63 times lower IC50 value than that of cisplatin in HeLa cell line. The delivery system not only demonstrates enhanced cellular uptake but also shows a high drug e!ect which should diminish the associated side e!ects. Furthermore, a new, easy and inexpensive #uorescent based Pt quanti$cation method has been adopted instead of the commonly used ICP-based quanti$cation method and this strategy of quanti$cation could be elaborated to monitor#uorescent prodrug nanoparticles during real-time diagnosis.