DSPE-PEG-GPC3 修饰提升脂质-PEI 纳米颗粒的肝细胞特异性

文献：GPC3修饰脂质聚合物SiRNA递送系统的构建

链接：https://www.benthamdirect.com/content/journals/cpd/10.2174/0113816128258852231204102044

作者：  孙丹丹、 李晓宇、 刘亚茹、 全吉山 、 金光宇

DOI： https ://doi.org/10.2174/0113816128258852231204102044

背景：基因*因其*的*机制而备受关注，然而由于缺乏安全有效的载体，其在临床上尚未得到广泛应用。磷脂酰肌醇聚糖3 (GPC3) 是一种对肝细胞癌具有高度特异性的蛋白多糖，是肝细胞癌诊断和*的潜在靶点。为了监测基因*效果并提高基因载体的转染效率，本研究制备了一种可视化的肝脏靶向siRNA（小干扰RNA）载体——GPC3修饰的脂质聚乙烯亚胺修饰的超顺磁性纳米粒子 (GLPS)。方法：通过体外基因沉默、细胞毒性试验和琼脂糖凝胶电泳，筛选出最佳的GLPS制剂。体外MRI和普鲁士蓝染色验证了GLPS的肝靶向性。我们还通过与兔红细胞共培养分析了GLPS的生物相容性。HE染色评估了GLPS的形态学变化。结果：GLPS最佳配方为LPS与siRNA质量比25:1，LPS与DSPE-PEG-GPC3摩尔比2:3。GLPS表现出明显的肝靶向性。体外实验中，共培养未见红细胞形态学改变及溶血现象。体内实验中，注射GLPS后，常规血液分析未见异常。肾脏、脾脏和肝脏组织形态正常，未见损伤及炎症反应。结论：GLPS有望成为一种有效的肝靶向MRI监测及siRNA递送载体。

Background: Gene therapy has been widely concerned because of its unique therapeutic mechanism. However, due to the lack of safe and effective carries, it has not been widely used in clinical practice. Glypican 3 (GPC3) is a highly specific proteoglycan for hepatocellular carcinoma and is a potential diagnostic and therapeutic target for hepatocellular carcinoma. Herein, to monitor the effect of gene therapy and enhance the transfection efficiency of gene carriers, GPC3-modified lipid polyethyleneimine-modified superparamagnetic nanoparticle (GLPS), a type of visualized carrier for siRNA (small-interfering RNA) targeting the liver, was prepared. Methods: We performed in vitro gene silencing, cytotoxicity, and agarose gel electrophoresis to identify the optimal GLPS formulation. In vitro MRI and Prussian blue staining verified the liver-targeting function of GLPS. We also analyzed the biocompatibility of GLPS by co-culturing with rabbit red blood cells. Morphological changes were evaluated using HE staining. Results: The GLPS optimal formulation consisted of LPS and siRNA at a mass ratio of 25:1 and LPS and DSPE-PEG-GPC3 at a molar ratio of 2:3. GLPS exhibited evident liver-targeting function. In vitro, we did not observe morphological changes in red blood cells or hemolysis after co-culture. In vivo, routine blood analysis revealed no abnormalities after GLPS injection. Moreover, the tissue morphology of the kidney, spleen, and liver was normal without injury or inflammation. Conclusion: GLPS could potentially serve as an effective carrier for liver-targeted MRI monitoring and siRNA delivery.

西安齐岳生物提供相关产品：

DSPE-PEG-cRGD

DSPE-PEG-KRWWKWWRR

DSPE-PEG-TAT

DSPE-PEG-CTT2

DSPE-PEG-CPP

DSPE-PEG-octreotide

DSPE-PEG-SP94

DSPE-PEG-CCK8

DSPE-PEG2000-GE11

DSPE-PEG2K-YIGSR

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