肿瘤转移是造成乳腺癌患者死亡的主要原因，转移性乳腺癌的治疗仍面临严峻挑战。本项目拟将紫杉烷类药物与乙酰肝素酶（Hpa）的底物—硫酸乙酰肝素共价连接，通过自组装形成胶束，并将抗转移药物（阿司匹林或双硫仑）和免疫检查点抑制剂（HY19991）共同包载于胶束内核，再从小鼠外周血中提取Ly6C高表达的单核细胞亚群，通过与单核细胞共孵育将上述载药胶束载入单核细胞中，设计构建基于单核细胞的肿瘤微环境响应性药物递释系统（HM@MC）。HM@MC可同时载入多种不同药物而不影响单核细胞的完整性和活性，因而可保留单核细胞天然的肿瘤靶向能力，不受肿瘤异质性的影响，易在原位肿瘤和转移灶富集，并在乳腺癌细胞过表达的Hpa的作用下释放药物，实现化疗与免疫治疗的协同增效。该项目思路新颖，有望在仿生药物递释系统抗转移性乳腺癌方面取得突破。

Metastasis is the main cause of death to breast cancer patients. The therapy of metastatic breast cancer still faces severe challenges. In this project, taxanes will be covalently linked to heparan sulfate, the substrate of heparanase (Hpa). The conjugate will self-assemble into micelles, which incorporate the anti-metastasis agent (Aspirin or disulfiram) and the immune checkpoint inhibitor (HY19991). The Ly6Chi monocytes will be separated from peripheral blood of mice, and load monocytes with drug-loaded micelles via phagocytosis to construct monocytes-based tumor microenvironment-responsive drug delivery system (HM@MC). HM@MC can be loaded with multiple drugs simultaneously without disrupt the integrity and activity of monocytes, thus maintain their instinctive tumor-targeting ability, which is independent of tumor heterogenicity. HM@MC can accumulate at primary tumor and metastases and release drugs under the action of Hpa, which is overexpressed in breast cancer cells, achieving synergism between chemotherapy and immune therapy. The idea is innovative, and it is expected to make breakthroughs anti-metastatic breast cancer by bionic drug delivery systems.