摘要
Enhancing the heat-sensitivity of tumor cells provides an alternative solution to maintaining the therapeutic outcome of photothermal therapy(PTT). In this study, we constructed a therapeutic system, which was composed of methoxy-polyethylene-glycol-coated-gold-nanorods(MPEG-AuN R) 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-AuN R mediated PTT combined with VER-155008-micelles. VER-155008-micelles downregulate 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 ℃ is equal to that treated with high temperature hyperthermia(55 ℃) in vitro. Furthermore, we proved either the MPEG-AuN R 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℃ mild PTT system, which contrasted to the tumor size when treated with individual 45℃ mild PTT(around 500nm^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.
Enhancing the heat-sensitivity of tumor cells provides an alternative solution to maintaining the therapeutic outcome of photothermal therapy(PTT). In this study, we constructed a therapeutic system, which was composed of methoxy-polyethylene-glycol-coated-gold-nanorods(MPEG-AuN R) 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-AuN R mediated PTT combined with VER-155008-micelles. VER-155008-micelles downregulate 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 ℃ is equal to that treated with high temperature hyperthermia(55 ℃) in vitro. Furthermore, we proved either the MPEG-AuN R 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℃ mild PTT system, which contrasted to the tumor size when treated with individual 45℃ mild PTT(around 500nm^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.
基金
financially supported by The 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)
