DSPE-PEG-GPC3 修飾提升脂質-PEI 納米顆粒的肝細胞特異性

文獻：GPC3修飾脂質聚合物SiRNA遞送系統的構建

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

作者：  孫丹丹、 李曉宇、 劉亞茹、 全吉山 、 金光宇

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

背景：基因*因其*的*機制而備受關注，然而由于缺乏安全有效的載體，其在臨床上尚未得到廣泛應用。磷脂酰肌醇聚糖3 (GPC3) 是一種對肝細胞癌具有高度特異性的蛋白多糖，是肝細胞癌診斷和*的潛在靶點。為了監測基因*效果并提高基因載體的轉染效率，本研究制備了一種可視化的肝臟靶向siRNA（小干擾RNA）載體——GPC3修飾的脂質聚乙烯亞胺修飾的超順磁性納米粒子 (GLPS)。方法：通過體外基因沉默、細胞毒性試驗和瓊脂糖凝膠電泳，篩選出最佳的GLPS制劑。體外MRI和普魯士藍染色驗證了GLPS的肝靶向性。我們還通過與兔紅細胞共培養分析了GLPS的生物相容性。HE染色評估了GLPS的形態學變化。結果：GLPS最佳配方為LPS與siRNA質量比25:1，LPS與DSPE-PEG-GPC3摩爾比2:3。GLPS表現出明顯的肝靶向性。體外實驗中，共培養未見紅細胞形態學改變及溶血現象。體內實驗中，注射GLPS后，常規血液分析未見異常。腎臟、脾臟和肝臟組織形態正常，未見損傷及炎癥反應。結論：GLPS有望成為一種有效的肝靶向MRI監測及siRNA遞送載體。

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.

西安齊岳生物提供相關產品：

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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