3 years ago

Cyclometalated Iridium(III)-Complex-Based Micelles for Glutathione-Responsive Targeted Chemotherapy and Photodynamic Therapy

Cyclometalated Iridium(III)-Complex-Based Micelles for Glutathione-Responsive Targeted Chemotherapy and Photodynamic Therapy
Hongzhong Chen, Jin-Gang Liu, Huijing Xiang, Huijun Phoebe Tham, Soo Zeng Fiona Phua, Yanli Zhao
The integration of chemotherapy and photodynamic therapy (PDT) in a single delivery system is highly desirable for enhancing anticancer therapeutic efficacy. Herein, two cyclometalated Ir(III) complex-constructed micelles FIr-1 and FIr-2 were demonstrated for glutathione (GSH) activated targeted chemotherapy and PDT. The cyclometalated Ir(III) complexes were prepared by conjugating phosphorescent Ir(III) compounds with chemotherapeutic drug camptothecin (CPT) through GSH responsive disulfide bond linkages, and the Ir(III) complexes were then assembled with amphiphilic surfactant pluronic F127 via noncovalent encapsulation to afford micelles. The surfaces of the micelles were further decorated with folic acid as a targeting group. The micelles showed intense fluorescence that renders them with excellent real-time imaging capability. The release of free anticancer drug CPT from the micelles was realized through GSH-activated disulfide bond cleavage in tumor cells. In addition, the micelles were capable of generating singlet oxygen used for PDT upon visible light irradiation. On account of having folic acid targeting ligand, the micelles displayed greater cellular accumulation in folate receptor (FR) overexpressed HeLa cells than FR low-expressed MCF-7 cells, leading to selective cancer cell killing effect. As compared with solo therapeutic systems, the micelles with targeted combinational chemotherapy and PDT presented superior potency and efficacy in killing tumor cells at a low dosage. On the basis of these findings, the multifunctional micelles could serve as a versatile theranostic nanoplatform for cancer cell targeted imaging and combinational therapy.

Publisher URL: http://dx.doi.org/10.1021/acsami.7b09506

DOI: 10.1021/acsami.7b09506

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