Engineering of multifunctional temperature-sensitive liposomes for synergistic photothermal, photodynamic, and chemotherapeutic effects

초록

Heterogeneity of cancer cells and drug resistance require multiple therapeutic approaches for comprehensive treatment. In this study, temperature-sensitive liposomes containing anti-cancer agent tanespimycin (17-AAG) and photosensitizer IR 820 were developed for combination of phototherapy and chemotherapy. The temperature-sensitive liposomes composed of DPPC, cholesterol, DSPE-PEG, 17-AAG, and IR 820 (LP-AI) at weight ratio of 35/15/3/2/2 were formulated as a thin film using extrusion and evaluated for particle size, morphology and drug release profile. Furthermore, the anticancer effect of combined therapy was examined in vitro and in vivo in SCC-7 and MCF-7 cell lines. As a result, LP-AI was prepared at particle size of 166.7 +/- 1.3 nm, PDI of 0.153 +/- 0.012, and zeta-potential of -32.6 +/- 0.8 mV. After NIR irradiation (660 and 808 nm laser), LP-AI could generate heat and ROS and enhance drug release from nanoparticles which were useful to kill the cancer cells. These were confirmed by in vitro cytotoxicity as well as in vivo effective ablation of tumors. In conclusion, fast drug release and enhanced treatment efficacy of LP-AI indicate the potential of integrating photo-and chemotherapy for synergistic anti-cancer effects. (c) 2017 Elsevier B.V. All rights reserved.

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