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甘露糖修饰的可生物降解聚乙烯亚胺用于树突状细胞的靶向 DNA 递送。

Mannosylated biodegradable polyethyleneimine for targeted DNA delivery to dendritic cells.

机构信息

Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of China.

出版信息

Int J Nanomedicine. 2012;7:2929-42. doi: 10.2147/IJN.S31760. Epub 2012 Jun 14.

DOI:10.2147/IJN.S31760
PMID:22745554
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3384368/
Abstract

BACKGROUND

To establish a potential gene-delivery system with the ability to deliver plasmid DNA to dendritic cells (DCs) more efficiently and specifically, we designed and synthesized a low-molecular-weight polyethyleneimine and triethyleneglycol polymer (PEI-TEG) and a series of its mannosylated derivatives.

METHODS

PEI-TEG was synthesized from PEI2000 and PEI600 with TEG as the cross-linker. PEI-TEG was then linked to mannose via a phenylisothiocyanate bridge to obtain man-PEI-TEG conjugates. The DNA conveyance abilities of PEI-TEG, man-PEI-TEG, as well as control PEI25k were evaluated by measuring their zeta potential, particle size, and DNA-binding abilities. The in vitro cytotoxicity, cell uptake, and transfection efficiency of these PEI/DNA complexes were examined on the DC2.4 cell line. Finally, a maturation experiment evaluated the effect of costimulatory molecules CD40, CD80, and CD86 on murine bone marrow-derived DCs (BMDCs) using flow cytometry.

RESULTS

PEI-TEG and man-PEI-TEG were successfully synthesized and were shown to retain the excellent properties of PEI25k for condensing DNA. Compared with PEI-TEG as well as PEI25k, the man-PEI-TEG had less cytotoxicity and performed better in both cellular uptake and transfection assays in vitro. The results of the maturation experiment showed that all the PEI/DNA complexes induced an adequate upregulation of surface markers for DC maturation.

CONCLUSION

These results demonstrated that man-PEI-TEG can be employed as a DC-targeting gene-delivery system.

摘要

背景

为了建立一种能够更有效、更特异递送达树突状细胞（DC）的质粒 DNA 的潜在基因传递系统，我们设计并合成了一种低分子量的聚乙烯亚胺和三乙二醇聚合物（PEI-TEG）及其一系列甘露糖化衍生物。

方法

PEI-TEG 是由 PEI2000 和 PEI600 通过 TEG 作为交联剂合成的。然后，PEI-TEG 通过苯异硫氰酸酯桥连接到甘露糖上，得到甘露糖化的 PEI-TEG 缀合物。通过测量它们的 ζ 电位、粒径和 DNA 结合能力来评估 PEI-TEG、甘露糖化的 PEI-TEG 以及对照的 PEI25k 的 DNA 传递能力。在 DC2.4 细胞系上检测这些 PEI/DNA 复合物的体外细胞毒性、细胞摄取和转染效率。最后，通过流式细胞术评估了共刺激分子 CD40、CD80 和 CD86 对鼠骨髓来源的 DC（BMDC）的成熟实验的影响。

结果

成功合成了 PEI-TEG 和甘露糖化的 PEI-TEG，并证明它们保留了 PEI25k 凝聚 DNA 的优异性能。与 PEI-TEG 和 PEI25k 相比，甘露糖化的 PEI-TEG 具有更低的细胞毒性，并且在体外细胞摄取和转染实验中表现更好。成熟实验的结果表明，所有的 PEI/DNA 复合物都能充分上调 DC 成熟的表面标志物。

结论

这些结果表明，甘露糖化的 PEI-TEG 可以作为一种 DC 靶向基因传递系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/2e6241b2069c/ijn-7-2929f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/582f69fb8c13/ijn-7-2929f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/418b022c9044/ijn-7-2929f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/b1bea7790374/ijn-7-2929f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/ec4232bab75b/ijn-7-2929f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/0a36f8b12a04/ijn-7-2929f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/61bec8f8a081/ijn-7-2929f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/68be2901f8fd/ijn-7-2929f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/062494af8895/ijn-7-2929f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/2e6241b2069c/ijn-7-2929f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/582f69fb8c13/ijn-7-2929f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/418b022c9044/ijn-7-2929f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/b1bea7790374/ijn-7-2929f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/ec4232bab75b/ijn-7-2929f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/0a36f8b12a04/ijn-7-2929f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/61bec8f8a081/ijn-7-2929f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/68be2901f8fd/ijn-7-2929f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/062494af8895/ijn-7-2929f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0176/3384368/2e6241b2069c/ijn-7-2929f9.jpg

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