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This work demonstrates the judicious application of a prodrug delivery strategy to achieve a highly improved anticancer drug effect of cisplatin using mesoporous silica nanoparticles. Our effort primarily addressed several pressing needs to overcome various impediments such as toxicity concerns, rapid inactivation, and low drug efficiency of cisplatin prodrug. The developed delivery system utilizes fluorescent 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 IC 50 value than that of cisplatin in HeLa cell line. The delivery system not only demonstrates enhanced cellular uptake but also shows a high drug effect which should diminish the associated side effects. Furthermore, a new, easy and inexpensive fluorescent based Pt quantification method has been adopted instead of the commonly used ICP-based quantification method and this strategy of quantification could be elaborated to monitor fluorescent prodrug nanoparticles during real-time diagnosis.

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