Pt(IV)-based Drug Delivery System Using Fluorescent Mesoporous Silica Nanoparticle

Abstract

Drug delivery systems for chemotherapy have been increasingly proposed as the method which has the benefits of improving anticancer efficacy and reducing adverse effects. Moreover the multi-functional drug delivery vector has facilitated the development of theragnostics, targeting drug delivery, and so on. Cisplatin (cis-[PtCl2(NH3)2](II)) is one of the most widely used anticancer agents because it plays an important role in the cure of various cancers such as testicular, ovarian, head and neck cancer. However, cisplatin is vulnerable to be attacked by plasma proteins such as serum albumin, resulting in less therapeutic efficacy and adverse effects. Therefore many research groups have been try to overcome these problems with finding new generation platinum-based drugs or applying to drug delivery systems. However, except several platinum related drugs, most of them were failed due to relatively low efficiency compared with cisplatin and also safety problems and in drug delivery system, loading of cisplatin is harder than that of other drugs due to the solubility issue and lack of functional group to conjugate with delivery vectors. To improve these problems, recently various Pt(IV)-based drugs oxidized from cisplatin have been developed. These have two additional coordination sites to be modified with various functional groups. These functional groups allow Pt(IV)-based drugs to increase the solubility and to conjugate with vectors. Moreover, these drugs have less toxicity in normal state, however, they are reduced to cisplatin in the reductive cellular environment resulting in regaining their anticancer efficiency. Cause of this reason, these Pt(IV)-based drugs are also called prodrugs. Herein, we used drug delivery system to have synergistic effect of safety from Pt(IV)-based drug and higher efficacy from delivery vector than cisplatin. As we used a vector of FITC-modified mesoporous silica nanoparticle for Pt(IV)-based drug delivery (Scheme 1.), there are several strong point like 62-fold increased anticancer efficacy than cisplatin and direct monitoring of vector position compared with other Pt(IV)-based drug delivery systems like gold nanoparticle so on. In addition, new platinum quantification system using fluorescent method was applied in this real system’s Pt quantification for more easy and non-expensive than the existing ICP-based quantification method.