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 130.8 ± 2.3 nm, 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.

KEYWORDS:

• Docetaxel
• indocyanine green
• hyperthermia
• low temperature-sensitive liposome
• near-infrared irradiation

Declaration of interest

The usual blurb will go after any declaration details The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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Additional information

Funding

This study was supported by the National Research Foundation of Korea (2015R1A2A2A01004118, 2015R1A2A2A04004806). This work was also supported by the Medical Research Center Program (2015R1A5A2009124) through the NRF funded by MSIP.