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

Abstract

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.

Turn-On Supramolecular Host-Guest Nanosystems as Theranostics for Cancer

“…72 Given the fact that its concentration in tumor cells is 100-to 1,000-fold higher than that in the extracellular microenvironment, GSH is an excellent promoter of selective intracellular drug release in tumor cells microenvironment. 73 Recently, Chen and co-workers 74 described a GSH-driven turn-on supramolecular theranostic nanosystem composed of a b-cyclodextrin-based polyrotaxane. The key design feature of this theranostic system, which displays dual-responsive drug release, and the details of its function are illustrated in Figure 10A.…”

Supramolecular Vesicles for Stimulus‐Responsive Drug Delivery

“…Their concentration levels have been proven to have an essential relationship to many diseases like cancer, liver damage, and Parkinson's disease. [68] For example, the concentration of GSH in cancerous cells is up to one thousand times higher than that in normal cells. This abnormal expression has been widely explored as a trigger for controlled drug release.…”

Iridium(III) Complex–Derived Polymeric Micelles with Low Dark Toxicity and Strong NIR Excitation for Phototherapy and Chemotherapy

“…[ 15 ] Despite these strengths, the clinical utilization of iridium(III) complexes has been delayed because of their poor water solubility, high dark toxicity, and weak absorption in the NIR region. [ 16–18 ] Hence, iridium(III) compound was attached to upconversion nanoparticles (UCNPs) to achieve NIR excitation. [ 19 ] Up till now, few examples have been reported to solve all these issues at once.…”