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 compose...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.展开更多
基金financially supported by The National Natural Science Fund for Distinguished Young Scholars (NSFC31525009)National Natural Science Foundation of China (31771096)+1 种基金Sichuan Innovative Research Team Program for Young Scientists (2016TD0004)Distinguished Young Scholars of Sichuan University (2011SCU04B18)
文摘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.
