经肝动脉化疗栓塞术是目前治疗肝癌的公认手段，但因目前缺乏理想的栓塞材料，致使肝癌介入治疗“栓而不死”，严重影响了介入治疗肝癌远期疗效。研究证实：抗糖酵解剂3-BrOP具有强大的抑制肿瘤能量代谢作用，但其体内应用仍缺乏合适的给药途径和高效的载体。而我们前期所研发的温敏纳米凝胶，既可作为一种智能型的液体栓塞剂，也可作为基因、蛋白和化疗药物的良好载体。因此本项目拟在前期工作基础上，构建碘油-纳米凝胶“胶囊”，于其内部负载抗肿瘤能量代谢药物，外部偶联肝癌靶向性蛋白。我们预期：经导管引入“纳米胶囊”后，与肿瘤微环境中相关因子靶向结合，释放抗能量代谢药物，并牢固栓塞肿瘤血管，实现对肿瘤能量代谢和微环境的多重靶向性协同治疗。本项目将开展体内外研究，借以影像学和分子生物学等多种手段评价疗效并阐明治疗机制，将以肿瘤能量代谢为靶点的从源头上调控微环境的治疗提供新策略。

Transcatheter arterial chemoembolization is the accepted means for treatment of liver cancer, but the embolic materials current use are still not ideal enough, and which are the significant cause of tumor recurrence after transcatheter arterial chemoembolization. Studies had demonstrated that 3-BrOP is a potently glycolytic inhibitor, but there still no suitable route of administration and efficient carrier for vivo applications. The temperature-sensitive nanogel dispersions we developed had been confirmed to be a new thermo sensitive liquid embolic agent and can be serve as vectors for drugs, proteins and gene. The project intends to prepare 3-BrOP-loaded-lipidol-PNIPAM based nanogels and modified with RGD peptides, which is a further exploration of our previous studies. We expect that the introduction of the "nanocapsules" in transcatheter method can targeted binding the factors in the tumor microenvironment and resulted in durable occlusion of the vessels，thus achieving tumor energy metabolism and microenvironment targeting multiple concurrent therapy. The project will be carried out in vivo and vitro to evaluate the efficacy and mechanism, through molecular biology and Medical Imaging way, and will provide a new treatment strategy regulating the microenvironment from the source with target tumor energy metabolism.