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一种新型的 CAV 衍生穿膜肽可通过 caveolae 介导的内吞作用有效递外源性分子。

A novel CAV derived cell-penetrating peptide efficiently delivers exogenous molecules through caveolae-mediated endocytosis.

机构信息

Key Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China.

Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China.

出版信息

Vet Res. 2018 Feb 13;49(1):16. doi: 10.1186/s13567-018-0513-2.

DOI:10.1186/s13567-018-0513-2
PMID:29439726
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5812233/
Abstract

Cell-penetrating peptide (CPP) is a promising cargo for delivering bioactive molecules. In this study, the N terminus of VP1 from chicken anemia virus, designated as CVP1, was found to carry enriched arginine residues with α-helix. By confocal imaging, flow cytometry and MTT assay, we identified CVP1 as a novel, safe and efficient CPP. CVP1-FITC peptide could entry different types of cells tested with dose dependence, but without cytotoxic effects. Compared with TAT-FITC peptide, the CVP1-FITC peptide showed much higher cell-penetrating activity. Moreover, CVP1 could successfully deliver β-glycosidase, poly (I:C) and plasmid into HCT116 cells. Inhibitors and temperature sensitivity analysis further indicated that the cell-penetrating activity of CVP1 was based on ATP-dependent and caveolae-mediated endocytosis. All these data demonstrate that CVP1 has efficient cell-penetrating activity and great potential for developing a novel delivery vector.

摘要

细胞穿透肽(CPP)是一种很有前途的运载生物活性分子的载体。在这项研究中,我们发现来自鸡贫血病毒的 VP1 的 N 端,被命名为 CVP1,携带富含精氨酸残基的α-螺旋。通过共聚焦成像、流式细胞术和 MTT 检测,我们鉴定出 CVP1 是一种新型、安全、高效的 CPP。CVP1-FITC 肽可以剂量依赖地进入不同类型的细胞,但没有细胞毒性作用。与 TAT-FITC 肽相比,CVP1-FITC 肽具有更高的细胞穿透活性。此外,CVP1 能够成功地将β-葡糖苷酶、聚(I:C)和质粒递送至 HCT116 细胞。抑制剂和温度敏感性分析进一步表明,CVP1 的细胞穿透活性是基于 ATP 依赖性和小窝蛋白介导的内吞作用。所有这些数据表明 CVP1 具有有效的细胞穿透活性,为开发新型递药载体提供了巨大的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/635ee855d017/13567_2018_513_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/e3af26c7edc4/13567_2018_513_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/c252135a5d4b/13567_2018_513_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/ed8c506a63e5/13567_2018_513_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/a79f7908b4b2/13567_2018_513_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/edc23c71e080/13567_2018_513_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/7d70b67233e5/13567_2018_513_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/635ee855d017/13567_2018_513_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/e3af26c7edc4/13567_2018_513_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/c252135a5d4b/13567_2018_513_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/ed8c506a63e5/13567_2018_513_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/a79f7908b4b2/13567_2018_513_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/edc23c71e080/13567_2018_513_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/7d70b67233e5/13567_2018_513_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cee/5812233/635ee855d017/13567_2018_513_Fig7_HTML.jpg

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