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Enhancing the heat-sensitivity of tumor cells provides an alteative 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-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 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 1C is equal to that treated with high temperature hyperthermia (55 1C) 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 100mm3 or vanished) when treated with combing 45 1C mild PTT system, which contrasted to the tumor size when treated with individual 45 1C mild PTT (around 500 nm3) or normal saline as control (larger than 2000 nm3). 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.