Incorporation of chemotherapeutic agent and photosensitizer in a low temperature-sensitive liposome for effective chemo-hyperthermic anticancer activity

Abstract

Objectives: In this study, we combined chemo- and hyperthermia therapy in a low temperature-sensitive liposome (LTSL) for potential cancer treatment. Methods: Docetaxel (DOC) and indocyanine green (ICG) as a therapeutic agent and photosensitizer, respectively, were incorporated in a low temperature-sensitive liposome (LTSL/DI). Nanoparticles were evaluated for the physicochemical characterizations, in vitro uptake and cytotoxicity, and furthermore in vivo anticancer activity. Results: The particle size of LTSL/DI was 130.82.3nm, and its drug release profile was pH- and temperature-dependent, which are effective for tumor targeting. The in vitro anticancer activity of LTSL/DI was significantly enhanced compared with free DOC in SCC-7 and MCF-7 cell lines. Interestingly, near-infrared laser irradiation after the treatment resulted in better anticancer activity than in the non-irradiated condition. The in vivo tumor regression effect of LTSL/DI in combination with NIR irradiation was much greater compared with the control group in SCC-7 tumor-bearing mice. After intratumoral injection of LTSL/DI, local heat induced by NIR irradiation and the localized docetaxel burst release could completely ablate the tumor, and inhibit its recurrence. Conclusions: These results suggest LTSL/DI formulation as a potential therapeutic strategy with effectively localized anti-tumor activity and low risk of side effect to non-target organs.