光动力治疗(PDT)是肝门部胆管癌的姑息治疗新手段，但传统光敏剂(PSs)在聚集时效率下降且对肿瘤灶无靶向性。我们研究证实负载AIE PSs的纳米药物弥补上述缺陷且疗效明确，但也致HIF-1a表达上调，为肿瘤的复发转移埋下隐患。为此，我们设想：以靶向纳米载体为工具，运载线粒体靶向的AIE-Mito PSs和HIF-1a抑制剂LW6，PDT杀灭癌细胞同时阻断HIF-1a信号通路可能是一种高效的协同治疗方案。. 本项目拟采用对pH响应的纳米载体，借助EPR效应进入肿瘤灶(组织靶向)，cRGD介导纳米药物靶向进入癌细胞内(细胞靶向)，溶酶体酸性环境促发纳米结构解体，释放出AIE-Mito PSs特异结合于线粒体(细胞器靶向)，光照下发挥PDT作用，且LW6阻断PDT所致的HIF-1a信号通路激活(分子靶向)，从组织、细胞、细胞器和分子的多水平靶向治疗肝门部胆管癌，为其提供新的治疗策略。

Photodynamic therapy (PDT) is a novel palliative treatment for hilar cholangiocarcinoma. However, the efficacy of traditional photosensitizer (PSs) is reduced when they accumulate, and there is no targeting to tumor foci. Our previous study demonstrated the nano-drug loaded PSs with aggregation-induced emission characteristics (AIE PSs) could overcome the above-mentioned drawbacks, but the level of hypoxia-inducible factor-1a (HIF-1a) was up-regulated after PDT, which resulted in risk of the recurrence and metastasis of tumor. Therefore, we hypothesize that combination PDT with inhibition of HIF-1a signal pathway perhaps is a high efficient synergetic treatment, through carrying mitochondria-specific AIE-Mito PSs and HIF-1a inhibitor LW6 into cholangiocarcinoma cells mediated by targeting nanocarrier. . In this research, the nano-drug system will be carried by pH-responsive vector, accumulated into tumor foci (targeting in tissue level), internalized nano-drug into targeted cells mediated by cRGD (targeting in cell level), triggered to disintegration of nanostructures by acid lysosome, and release the AIE-Mito PSs and LW6. Then, the AIE-Mito PSs specifically bind to mitochondria (targeting in organelle level) and play a role in PDT effect. Meanwhile, the LW6 inhibit the HIF-1a signal pathway caused by PDT (targeting in molecular level). Thus this research aim at provide a novel treatment strategy for hilar cholangiocarcinoma via multi-level targeting of tissue, cell, organelle and molecule.