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Mitochondria-targeting Near-infrared Light-triggered Thermosensitive Liposomes for Localized Photothermal and Photodynamic Ablation of Tumors Combined with Chemotherapy

Abstract

Lonidamine, as an anticancer drug that acts on mitochondria, has poor water solubility. Mitochondria are the primary source of cellular reactive oxygen species (ROS), which are necessary for photodynamic therapy. Hence, a mitochondria-targeting drug delivery system loaded with Lonidamine and ROS-produced photosensitizer could improve bioavailability of Lonidamine and maximize photodynamic therapeutic efficiency. Here we report, for the first time, the new IR-780 and Lonidamine encapsulated mitochondria-targeting thermosensitive liposomes IL-TTSL. DSPE-PEG2000-NH2 was coupled with triphenylphosphine to form DSPE-PEG2K-TPP. The liposomes IL-TTSL were self-assembled from DPPC, DSPC, DSPE-PEG2K-TPP, cholesterol, IR-780 and Lonidamine. Coupled linker modified triphenylphosphine (TPP) are cationic and can selectively accumulate several hundred-fold within mitochondria. Once the liposomes located inside mitochondria, 808 nm laser irradiation could trigger photosensitizer IR-780 to elevate local temperature, which could utilize in photothemal therapy and induce the release of Lonidamine from the thermosensitive liposomes. Meanwhile, IR-780 could release ROS for photodynamic therapy in mitochondria and increase photodynamic therapeutic efficiency. Our results showed that surface modification of the liposomes with triphenylphosphine cations had good mitochondria-targeting ability. The liposomes exhibited good biocompatibility and all the components of the empty liposomes were safe used in human. Few reports were related to IR-780 using in photodynamic therapy and we proved this function of IR-780. Overall, the stealth liposomes provide a new promising strategy to realize mitochondria-targeting thermosensitive chemo-, photodynamic and photothermal combination therapy with a single light source for lung cancer.

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Publication details

The article was received on 28 Mar 2017, accepted on 22 Jun 2017 and first published on 04 Jul 2017


Article type: Paper
DOI: 10.1039/C7NR02193C
Citation: Nanoscale, 2017, Accepted Manuscript
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    Mitochondria-targeting Near-infrared Light-triggered Thermosensitive Liposomes for Localized Photothermal and Photodynamic Ablation of Tumors Combined with Chemotherapy

    C. Yue, Y. Yang, J. Song, G. Alfranca, C. Zhang, Q. Zhang, T. Yin, F. Pan, J. Martinez de la Fuente and D. Cui, Nanoscale, 2017, Accepted Manuscript , DOI: 10.1039/C7NR02193C

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