Journal
ACTA PHARMACEUTICA SINICA B
Volume 8, Issue 4, Pages 587-601Publisher
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2018.05.011
Keywords
Tumor inhibitor; VER-155008; Micelle; Phototherapy; Gold nanorods
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Funding
- National Natural Science Fund for Distinguished Young Scholars [NSFC31525009]
- National Natural Science Foundation of China [31771096]
- Sichuan Innovative Research Team Program for Young Scientists [2016TD0004]
- Distinguished Young Scholars of Sichuan University [2011SCU04B18]
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Enhancing the heat-sensitivity of tumor cells provides an alternative solution to maintaining the therapeutic outcome of photothermal therapy (PIT). hi this study, we constructed a therapeutic system, which was composed of methoxy-polyethylene-glycol-coated-gold-nanorods(MPEG-AuNR) and VER-155008-micelles, to evaluate the effect of VER-155008 on the sensitivity of tumor cells to heat, and further investigate the therapeutic outcome of MPEG-AuNR mediated PIT combined with VER-155008-micelles. VER-155008-micelles down regulate the expression of heat shock proteins and attenuate the heat-resistance of tumor cell. The survival of HCT116 cells treated with VER-155008-micelles under 45 degrees C is equal to that treated with high temperature hyperthermia (55 degrees C) in vitro. Furthermore, we proved either the MPEG-AuNR or VER-155008-micelles can be accumulate in the tumor site by photoacoustic imaging and fluorescent imaging. In vivo anti-cancer evaluation showed that tumor size remarkably decreased (smaller than 100 mm(3) or vanished) when treated with combing 45 degrees C mild PIT system, which contrasted to the tumor size when treated with individual 45 degrees C mild PIT (around 500 nm(3)) or normal saline as control (larger than 2000 nm(3)). These results proved that the VER-155008-micelles can attenuate the heat-resistance of tumor cells and enhance the therapeutic outcome of mild-temperature photothermal therapy. (C) 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
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