阻止肿瘤转移是有效治疗肿瘤的重要策略。本研究旨在针对肿瘤转移进程中的关键事件——上皮间质转化和肿瘤新生血管，结合肿瘤微环境特征，构建一种新型载药脂质复合物，并研究其抗乳腺癌转移的效应与机制。首先利用基质金属蛋白酶（MMP）底物肽作为连接臂，合成穿膜肽双向修饰的功能化聚乙二醇；然后将其两端通过静电力作用锚定在载miRNA脂质体的表面，构建肿瘤微环境响应型脂质复合物。该脂质复合物表面的水化膜薄而紧致，在体内可避免被快速清除，到达肿瘤组织后在MMP作用下脱去水化膜，缩小粒径并暴露穿膜肽分子，提高肿瘤组织渗透性和细胞摄取效率。此外，该脂质复合物联合包载基因药、小分子调节剂和化疗药，可发挥不同机制药物的协同增效作用，以期实现控制肿瘤生长、遏制肿瘤转移的治疗目标。因此，本研究有望探索出一种新的肿瘤微环境响应型药物递送体系，并为抗肿瘤转移提供一种可能的联合用药方案，具有重要的学术意义和潜在的临床价值。

Inhibiting tumor metastasis is an important strategy for effective treatment of tumors. The objective of this study is to develop a kind of tumor microenvironment responsive lipoplexes, which are supposed to anti-metastasis by regulating epithelial-mesenchymal transition (EMT) and tumor angiogenesis. Firstly, with a matrix metalloproteinase (MMP) substrate peptide as a connecting arm, a kind of cell-penetrating peptide (CPP) bi-directional modified PEG is synthesized, which is subsequently anchored on the surface of the miRNA loaded liposomes, thus preparing tumor microenvironment responsive lipoplexes. The hydration shell of the lipoplexes surface would be thin and compact due to the bi-directional anchoring of PEG. The lipoplexes could avoid being quickly cleared in body, and once arriving at tumor tissues, the PEG chain on the surface of lipoplexes could be taken off by overexpressed MMP, leading to smaller particle sizes and explosion of CPP, which could further enhance its tumor tissue permeability and tumor cell uptake. In addition, the lipoplexes could load gene drug, small molecule modulator and chemotherapeutic drug in the same time, which means a synergic effect would be expected in curbing tumor volume and metastasis. Consequently, this study is going to explore a new kind of tumor microenvironment responsive drug delivery system and to offer a possible combination regimen for treatment of tumor metastasis. Hence, this study has important academical significance and potential value of clinical application.