title: Water-dispersible fullerene aggregates as a targeted anticancer prodrug with both chemo- and photodynamic therapeutic actions.
abstract: Prodrug therapy is one strategy to deliver anticancer drugs in a less reactive manner to reduce nonspecific cytotoxicity. A new multifunctional anticancer prodrug system based on water-dispersible fullerene (C60) aggregates is introduced; this prodrug system demonstrates active targeting, pH-responsive chemotherapy, and photodynamic therapeutic (PDT) properties. Incorporating (via a cleavable bond) an anticancer drug, which is doxorubicin (DOX) in this study, and a targeting ligand (folic acid) onto fullerene while maintaining an overall size of approximately 135 nm produces a more specific anticancer prodrug. This prodrug can enter folate receptor (FR)-positive cancer cells and kill the cells via intracellular release of the active drug form. Moreover, the fullerene aggregate carrier exhibits PDT action; the cytotoxicity of the system towards FR-positive cancer cells is increased in response to light irradiation. As the DOX drug molecules are conjugated onto fullerene, the DOX fluorescence is significantly quenched by the strong electron-accepting capability of fullerene. The fluorescence restores upon release from fullerene, so this fluorescence quenching-restoring feature can be used to track intracellular DOX release. The combined effect of chemotherapy and PDT increases the therapeutic efficacy of the DOX-fullerene aggregate prodrug. This study provides useful insights into designing and improving the applicability of fullerene for other targeted cancer prodrug systems.
authors.affiliation: College of Materials Science & Engineering, State Key Laboratory of Luminescent, Materials and Devices, South China University of Technology, Guangzhou 510640, PR China.
authors.forename: Jianquan
authors.initials: J
authors.lastname: Fan
authors.forename: Gang
authors.initials: G
authors.lastname: Fang
authors.forename: Fang
authors.initials: F
authors.lastname: Zeng
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wang
authors.forename: Shuizhu
authors.initials: S
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D037741:Fullerenes / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D010778:Photochemotherapy; D011355:Prodrugs / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D037741:Fullerenes; D011355:Prodrugs; D014867:Water