RGERPPR多肽，是肿瘤细胞和肿瘤血管内皮细胞表面均高表达受体NRP-1特异性配体，具有穿透肿瘤血管壁和肿瘤组织的能力，可携载多功能胶束递送系统突破肿瘤血管屏障和基质屏障，发挥多角度协同抗肿瘤作用。项目基于挑战肿瘤异质性，采用“RGERPPR介导靶向”策略，首次合成共聚物“甲基聚乙二醇-S-S-聚己内酯-线性聚乙烯亚胺(mPEG-S-S-PCL-IPEI)”与“TPGS2K-多肽”，构建一种多功能胶束递送系统，靶向输送化疗药物阿霉素（DOX）和肿瘤抑制基因上调因子miR-140 mimics。以期达到：静脉注射后，该系统在血液中稳定存在，靶向渗入到整个肿瘤组织，在高浓度的GSH作用下，还原敏感释放药物与调控基因，功能性载体（TPGS）发挥逆转多药耐药（MDR）作用。为解决肿瘤MDR和基因突变等异质性问题提供新途径，为肿瘤基因治疗递送系统研究及以miRNA为靶点的肿瘤分子治疗提供实验依据。

NRP-1 is a receptor overexpressed on both the tumour cells and the tumor endothelium. RGERPPR peptide, is a tumor-penetrating peptide, the specific ligand of NRP-1, is able to penetrate through tumor vessels and tumor tissues. It could act as the carrier of the micellar delivery system for penetrating tumor vessels barrier and matrix to achieve the synergistic antitumor effect. In order to challenge the tumor heterogeneity, we adopt the “RGERPPR mediated targeting” strategy. In our study, the new copolymers: methyl polyethylene glycol-S-S-poly-ε-caprolactone-I-polyethylenimine(mPEG-S-S-PCL-IPEI) and TPGS2K-RGERPPR, that was first synthesized by us, were used to prepare the DOX/miRNA-140 mimics micelle co-delivery system. The study was conducted to verify our hypothesis that, after the intravenous administration, the prepared micelle would specifically bind to NRP-1 and fracture disulfide bond through the reduction effect to reverse the drug releasing process and the process of gene regulation. The aim of this study is to discover a new way of explaining the tumor heterogeneity, such as MDR and gene mutation, and to provide experimental evidence for the study of tumor gene therapy delivery system and the molecular therapy of miRNA.