Among various methods, the use of targeting nucleic acid therapy is a promising method for inhibiting gastric cancer (GC) cells' rapid growth and metastasis abilities. In this study, vitamin B12-labeled poly (d,l-lactide-co-glycolide) and polyethylene glycol nanoparticles (PLGA-PEG-VB12 NPs) were developed for microRNAs-532-3p mimics incorporating as targeting gene delivery systems (miR-532-3p@PLGA-PEG-VB12 NPs) to fight against transcobalamin II (CD320)-overexpressed GC cells' progression. The PLGA-PEG-VB12 NPs with appropriate particle sizes and good bio-compatibility could be selectively delivered into CD320-overexpressed GC cells, and significantly decrease the expression of apoptosis repressor with caspase recruitment domain (ARC). Following that, more pro-apoptotic protein (Bax) flowed from cytoplasm into mitochondria to form Bax oligomerization, thus induced mitochondrial damage, including mitochondrial membrane potentials (MMPs) loss and excessive production of mitochondrial reactive oxygen species (mitoROS). Since that, mitochondrial permeability transition pore (mPTP) was opened, followed by induced more cytochrome c (Cyto C) releasing from mitochondria into cytosol, and finally activated caspase-depended cell apoptosis pathway. Therefore, our designed miR-532-3p@PLGA-PEG-VB12 NPs showed enhanced GC targeting ability, and could induce apoptosis through activating ARC/Bax/mitochondria-mediated apoptosis signaling pathway, finally remarkably suppressed proliferation of GC cells both in vitro and in vivo, which presented a promising treatment for GC.

在各种方法中，靶向核酸疗法的使用是抑制胃癌（GC）细胞快速生长和转移能力的有前途的方法。在这项研究中，维生素B12标记的聚（d，升-lactide-共-乙交酯）和聚乙二醇纳米粒子（PLGA-PEG-VB12 NPs）用于microRNAs-532-3p模拟物，并结合了靶向基因传递系统（miR-532-3p @ PLGA-PEG-VB12 NPs）以对抗反钴胺素II（ CD320）过度表达GC细胞的进程。具有适当的粒径和良好的生物相容性的PLGA-PEG-VB12 NPs可以选择性地传递到CD320过表达的GC细胞中，并显着降低具有胱天蛋白酶募集结构域（ARC）的细胞凋亡抑制因子的表达。之后，更多的促凋亡蛋白（Bax）从细胞质流入线粒体以形成Bax寡聚化，从而引起线粒体损伤，包括线粒体膜电位（MMPs）损失和线粒体活性氧（mitoROS）的过量产生。因为，c（Cyto C）从线粒体释放到细胞质中，并最终激活了依赖caspase的细胞凋亡途径。因此，我们设计的miR-532-3p @ PLGA-PEG-VB12 NPs显示出增强的GC靶向能力，并可以通过激活ARC / Bax /线粒体介导的凋亡信号通路来诱导凋亡，最终显着抑制了GC细胞在体外和体外的增殖。体内，这为GC提供了一种有希望的治疗方法。