见血封喉苷H（ToxH）是我们从海南热带植物见血封喉乳汁中分离并进行了结构鉴定的新化合物。在前期国家自然科学基金的资助下，我们发现ToxH 对多种肿瘤细胞具有较强的细胞毒活性，能同时诱导肿瘤细胞凋亡和自噬，展现出了可喜的转化应用前景。但是，ToxH不溶于水，不能直接制成水溶剂应用。为了解决这一难题，本项目拟以牛血清蛋白、叶酸、聚乙二醇为材料，制备一个载有ToxH并溶于水的靶向纳米载体，对这一载体进行表征和理化特性测定后，从体外细胞和小鼠体内两个层面开展研究，了解这一载体与肿瘤细胞靶向结合的特异性，分析所载药物ToxH在体内分布的特征（药代动力学），是否能靶向治疗肿瘤等。最后，利用分子生物学技术和方法了解ToxH 是否通过改变肿瘤免疫抑制的微环境，是否诱导肿瘤细胞免疫原性死亡等达到治疗肿瘤的作用，为更好转化开发ToxH成为自主知识产权的肿瘤治疗药物提供理论依据。

Toxicarioside H (ToxH) is a new cardenolide chemical compound isolated from the latex of Antiaris toxicaria in tropical Hainan Island. Based on a previous surport from the National Natural Science Foundation of China, Its structure was elucidated by our research group and showed significant cytotoxicity against K562,SGC-7901, SMMC-7721 and HeLa cell lines in vitro by MTT assay. In addition, we also found that ToxH can induce strong apoptosis and autophagy in several hepatoma carcinoma cells, indicating a potential translational prospect for clinical useage in the future. However, we found that ToxH is water insoluble, which indicate that it can not be developed as a solube injection by routine methods.To overcome this disadvantage, we will, in this study, prepare a nano-drug carrier, in which ToxH will be specially carried (ToxhFaBsa) to the tumor cells expressing folic acide receptor. The nano-carrier ToxhFaBsa is prepared based on the mixture materials of BSA polypeptides, folic acide and polyethylene glycol (PEG). Thereafter, we will detailedly analys its phyical and chemical characteristics, analys whether the ToxhFaBsa can effectively load and deliver the water insoluble drug ToxH to the tumor cells in vitro and in vivo. Furthermore,in this study, we will apply in vitro assays to acknowledge the capabilities of ToxhFaBsa in inhibition of tumor cell proliferation and induction of tumor cell apoptosis and immunogenic cell death in comparison with the control nano-carriers. High-performance liquid chromatography will be used to observe the biodistribution of the ToxhFaBsa in tumor-bearing mice. The antitumor activities of the ToxhFaBsa will be investigated in several murine tumor models. The change of the tumor microenvironment of ToxhFaBsa treatment will be investigated, and the evidence and possible molecular mechanism of the tumor immunogenic cell death will be specially investigated in tumor tissues and mice treated with ToxhFaBsaL by immunohistological assays and PCR arrays. In addition, Western blot and ELISA will be used to prove whether ToxhFaBsaL cause cellular and humoral immunity in the treated mice. Our study will offer experimental data for ToxH to be developed as a novel anti-tumor compound.