化疗是胃癌术后防治复发的主要手段，但有效率低，主要原因是：药物难以靶向到达胃癌病灶且胃癌干细胞通过自噬抵抗化疗。因此，调控胃癌干细胞自噬是提高化疗敏感性的关键。本人在前期研究中发现microRNA-532-3p（miR-532-3p）在化疗敏感人群呈高表达，提示其可能是调控干细胞化疗抵抗的自噬靶点。为增强药物进入癌组织的能力，我们构建了具有胃癌靶向性的维生素B12受体通路纳米药物递送系统，为携载miR-532-3p靶向调控胃癌干细胞自噬提供了可能。预实验显示：携载miR-532-3p的维生素B12靶向纳米药物递送系统可负向调控GDNF家族蛋白α1、抑制自噬、增加胃癌干细胞化疗敏感性，但该体系的理化性质、安全性及作用机制尚未阐明。本研究将探索维生素B12受体靶向纳米药物递送系统携载自噬抑制剂miR-532-3p的合成技术，阐明其调节胃癌干细胞化疗敏感性的作用机制，为胃癌增敏化疗提供新思路。

Chemotherapy is the main treatment for the postoperative patients with gastric cancer, but its effective rate is relatively low. There are two main reasons accounting for the chemotherapy failure. Firstly, traditional drugs lacked of tumor-targeting abilities, which means the chemotherapy agents that selectively bind to cancer cells..Secondly, gastric cancer stem cells (GCSC) could resist chemotherapy through activating autophagy. Therefore, regulating the autophagy ability of GCSC would be the key way to improve chemosensitivity. In previous studies, we found that microRNA-532-3p (miR-532-3p) was highly expressed in chemotherapy-sensitive population, suggesting that miR-532-3p might be a potential autophagic target for regulating chemotherapy resistance of GCSC. In order to further enhance miR-532-3p’s ability for targeting gastric cancer, we constructed vitamin B12 (VB12)-receptor targeting nano-drug delivery systems (nano-DDSs), which provides possibility for carrying miR-532-3p into gastric cancer tissue, then regulating the GCSC’s autophagic abilities. Our Preliminary experiments showed that miR-532-3p loading VB12-receptor targeting nano-DDSs could effectively enter GCSC cells, reduce the expression of GFNR family receptor α1 (GFRA1), inhibit GCSC’s autophagic abilities, and finally increase their sensitivity to traditional chemotherapeutic drugs. However, the physical and chemical properties, bio-safety, and the possible mechanism of VB12-receptor targeting nano-DDSs have not been elucidated. In this study, we will explore the synthesis technology of miR-532-3p loading VB12 receptor-targeted nano-DDSs, then explore their role in regulating the chemosensitivity of GCSC and the underlying mechanism, which would be a optimization strategy for gastric cancer sensitization chemotherapy.