Journal
CANCER LETTERS
Volume 500, Issue -, Pages 41-50Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.12.028
Keywords
Mitochondria-targeted; Hsp90 inhibitor; IR780; Mild-temperature; Photothermal therapy
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Funding
- Natural Science Foundation of China [81527803, 81420108018, 31971292]
- National Key R&D Program of China [2018YFC0910601, 2019YFA0405603, 2018YFC0115900]
- Zhejiang Province Financial Support [LQ19H180004, LGF19C100001]
- Zhejiang Science and Technology Project [2019C03077]
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A novel photosensitizer with mitochondrial targeting based on IR780 iodide and a heat shock protein 90 inhibitor (BIIB021) was synthesized, showing promising potential for reducing cell tolerance to heat and enhancing the effect of mitochondria-targeted mild-temperature photothermal therapy.
Mitochondria-targeted mild-temperature photothermal therapy (MT-PTT) is a promising strategy that can maximize anticancer effects and reduce adverse reactions. Here, a novel photosensitizer with mitochondrial targeting based on IR780 iodide and heat shock protein 90 inhibitor (BIIB021), which can passively accumulate in MCF-7 cells and achieve effective MT-PTT effect is synthesized. The prepared PEG-IR780-BIIB021 nano-micelles possess considerable biocompatibility and biological stability, with an encapsulation efficiency of about 84% for BIIB021. They can selectively enrich in mitochondria, and release BIIB021 after NIR irradiation to reduce cell tolerance to heat, thereby reducing the mitochondrial membrane potential and rapidly affecting key intrinsic apoptotic factors (Cyt-C, Caspase-9, Bcl-2 and Bax) to achieve the effect of MT-PTT. It is believed that mitochondria-targeted MT-PTT generated by the PEG-IR780-BIIB021 nano-micelles is a promising therapeutic strategy in clinical practice.
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