恶性黑色素瘤（MM）侵袭性高，治疗难度大，目前化疗和生物治疗都存在诸多不足。课题组前期研究发现，中药雷公藤主要有效成分雷公藤甲素（TPL）可抑制MM增殖，但如何将TPL靶向递送到MM组织，是充分发挥其作用的关键。本项目将仿生学概念引入中药纳米靶向给药系统研究，以MM细胞表面高表达的DR5受体作为靶点，利用基因重组技术，构建可天然靶向MM表面DR5受体的DR5mAb-Exo外泌体纳米靶向载体。利用DR5mAb-Exo内在的磷脂双分子层包载TPL，制备靶向MM组织、协同增效治疗MM纳米递送系统DR5mAb-Exo/TPL，将DR5mAb与TPL联用，实现双通路阻断抑制MM作用。并进一步阐明TPL与DR5mAb协同调控MM细胞侵袭作用机理、细胞内转运、降解机制、体内分布特征及抑癌效果。本项目的研究，有望为TPL治疗MM的制剂学研究开辟新途径，为中药抗肿瘤靶向给药系统设计提供实验基础和和方法借鉴。

Malignant melanoma (MM) is highly invasive and very difficult to treat. There are many deficiencies in both chemotherapy and biological therapy at present. Our previous studies found that triptolide (TPL), the main active ingredient of Tripterygium wilfordii, can inhibit MM proliferation. However, the targeted delivery of TPL to MM limits its therapeutic effect. In this study, bionics concept is introduced into the research of nanoparticle targeting drug delivery system. The high expression of DR5 receptor on the surface of MM cells was used as a target. We use gene recombination technology to construct a DR5mAb-Exo nanoparticle targeting carrier, targeting DR5 on the surface of MM. TPL was loaded in the DR5mAb-Exo internal phospholipid bilayer to prepare the DR5mAb-Exo/TPL delivery system, which can targeted MM tissue and synergistic effect to treat MM. DR5mAb and TPL were used to achieve double channel blocking and inhibit MM. In addition, the synergistic mechanism of TPL and DR5mAb to regulate the invasion of MM cells, intracellular transport, degradation mechanism, distribution in vivo, and the effect of cancer suppression were further investigated. .The project is expected to open up a new way for the preparation of TPL for the treatment of MM, and provide experimental basis and methods for the design of anti-tumor Chinese medicine target drug delivery system.