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
Nanotechnology-based photothermal therapy has attracted great attention in the past decade. Nevertheless, photothermal therapy has some inherent drawbacks, such as the uneven heat production and limited laser penetrat...Nanotechnology-based photothermal therapy has attracted great attention in the past decade. Nevertheless, photothermal therapy has some inherent drawbacks, such as the uneven heat production and limited laser penetration, often leading to insufficient treatment outcomes. Here, we developed a combination strategy to improve cancer therapy. The biomimetic albumin-modified gold nanorods(AuNRs) were prepared with incorporation of paclitaxel(PTX). This therapeutic system was characterized by several features. First, the albumin modification enhanced the biocompatibility and colloidal stability. Second, the surface-coated albumin promoted cellular uptake via the albumin-binding protein pathway. Third, PTX was incorporated via hydrophobic interaction between PTX and the albumin lipophilic domain. Fourth, the system can be used for combined photothermo-chemotherapy for yielding synergistic effects. The antitumor activity of the system was evaluated both in vitro and in vivo using the HCT116 colon cancer cell and tumor model. The combination therapy was found with an enhanced treatment efficiency and no obvious side effect. Most importantly, the thermal effect was also discovered with the ability to modulate the tumor microenvironments and suppress the macrophages polarization towards the M2 pro-tumor phenotype. It could be a mechanism for photothermal immunotherapy. The combination strategy and the system provide a potential method for cancer 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.
基金the National Basic Research Program of China (973 Program 2014CB931900 and 2013CB932503)NSFC, China (81373357, 81422048, 81673382 and 81521005) for the supportNational Center for Protein Science Shanghai, CAS, for the technical support at Electron Microscopy Facility
文摘Nanotechnology-based photothermal therapy has attracted great attention in the past decade. Nevertheless, photothermal therapy has some inherent drawbacks, such as the uneven heat production and limited laser penetration, often leading to insufficient treatment outcomes. Here, we developed a combination strategy to improve cancer therapy. The biomimetic albumin-modified gold nanorods(AuNRs) were prepared with incorporation of paclitaxel(PTX). This therapeutic system was characterized by several features. First, the albumin modification enhanced the biocompatibility and colloidal stability. Second, the surface-coated albumin promoted cellular uptake via the albumin-binding protein pathway. Third, PTX was incorporated via hydrophobic interaction between PTX and the albumin lipophilic domain. Fourth, the system can be used for combined photothermo-chemotherapy for yielding synergistic effects. The antitumor activity of the system was evaluated both in vitro and in vivo using the HCT116 colon cancer cell and tumor model. The combination therapy was found with an enhanced treatment efficiency and no obvious side effect. Most importantly, the thermal effect was also discovered with the ability to modulate the tumor microenvironments and suppress the macrophages polarization towards the M2 pro-tumor phenotype. It could be a mechanism for photothermal immunotherapy. The combination strategy and the system provide a potential method for cancer therapy.
