DSPE-PEG-GPC3 修飾提升脂質(zhì)-PEI 納米顆粒的肝細(xì)胞特異性

文獻(xiàn)：GPC3修飾脂質(zhì)聚合物SiRNA遞送系統(tǒng)的構(gòu)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(jī)制而備受關(guān)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(yīng)用。磷脂酰肌醇聚糖3 (GPC3) 是一種對(duì)肝細(xì)胞癌具有高度特異性的蛋白多糖，是肝細(xì)胞癌診斷和*的潛在靶點(diǎn)。為了監(jiān)測(cè)基因*效果并提高基因載體的轉(zhuǎn)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(zhì)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(xì)胞毒性試驗(yàn)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(lán)染色驗(yàn)證了GLPS的肝靶向性。我們還通過與兔紅細(xì)胞共培養(yǎng)分析了GLPS的生物相容性。HE染色評(píng)估了GLPS的形態(tài)學(xué)變化。結(jié)果：GLPS最佳配方為L(zhǎng)PS與siRNA質(zhì)量比25:1，LPS與DSPE-PEG-GPC3摩爾比2:3。GLPS表現(xiàn)出明顯的肝靶向性。體外實(shí)驗(yàn)中，共培養(yǎng)未見紅細(xì)胞形態(tài)學(xué)改變及溶血現(xiàn)象。體內(nèi)實(shí)驗(yàn)中，注射GLPS后，常規(guī)血液分析未見異常。腎臟、脾臟和肝臟組織形態(tài)正常，未見損傷及炎癥反應(yīng)。結(jié)論：GLPS有望成為一種有效的肝靶向MRI監(jiān)測(cè)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pg電子官方生物提供相關(guān)產(chǎn)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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