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聚丙交酯与聚乙烯亚胺的整合促进了安全有效的细胞内小干扰RNA递送。

Integration of Polylactide into Polyethylenimine Facilitates the Safe and Effective Intracellular siRNA Delivery.

作者信息

Ding Guo-Bin, Meng Xue, Yang Peng, Li Binchun, Stauber Roland H, Li Zhuoyu

机构信息

Institute of Biotechnology, the Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China.

Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, China.

出版信息

Polymers (Basel). 2020 Feb 14;12(2):445. doi: 10.3390/polym12020445.

DOI:10.3390/polym12020445
PMID:32074943
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7077636/
Abstract

Polyethylenimine (PEI) is a gold standard polymer with excellent transfection efficacy, yet its severe toxicity and nondegradability hinders its therapeutic application as a gene delivery vector. To tackle this problem, herein we incorporated the biodegradable polylactide (PLA) into the branched PEI by synthesizing a PEI-PLA copolymer via a facile synthetic route. PLA modification significantly improved the cytocompatibility of PEI, PEI-PLA copolymer showed much higher cell viability than PEI as verified in three different human cancer cell lines (HCT116, HepG2 and SKOV3). Interestingly, the PEI-PLA copolymer could effectively bind siRNA targeting PKM2, and the obtained polyplex displayed much higher stability in serum than naked siRNA as determined by agarose gel electrophoresis. Moreover, cellular uptake study demonstrated that PEI-PLA could efficiently deliver the Cy5-labled siRNA into the three tested cancer cell lines, and the transfection efficiency is equivalent to the commercial Lipofectamine 2000. Finally, it is noteworthy that the polyplex is comparable to Lipo2000 in down-regulating the expression of PKM2 at both mRNA and protein level as measured by q-PCR and western blotting, respectively. Overall, the PEI-PLA copolymer developed in this study has the potential to be developed as a versatile carrier for safe and effective delivery of other nucleic acid-based agents.

摘要

聚乙烯亚胺（PEI）是一种具有优异转染效果的金标准聚合物，但其严重的毒性和不可降解性阻碍了其作为基因递送载体的治疗应用。为了解决这个问题，我们通过简便的合成路线合成了PEI-聚乳酸（PLA）共聚物，将可生物降解的聚乳酸（PLA）引入到支链PEI中。PLA修饰显著提高了PEI的细胞相容性，在三种不同的人类癌细胞系（HCT116、HepG2和SKOV3）中验证，PEI-PLA共聚物的细胞活力比PEI高得多。有趣的是，PEI-PLA共聚物能够有效地结合靶向PKM2的小干扰RNA（siRNA），通过琼脂糖凝胶电泳测定，所得到的多聚体在血清中的稳定性比裸siRNA高得多。此外，细胞摄取研究表明，PEI-PLA能够有效地将Cy5标记的siRNA递送至三种受试癌细胞系中，其转染效率与市售的Lipofectamine 2000相当。最后，值得注意的是，通过实时定量聚合酶链反应（q-PCR）和蛋白质免疫印迹法分别测定，该多聚体在下调PKM2的mRNA和蛋白质表达水平方面与Lipofectamine 2000相当。总体而言，本研究中开发的PEI-PLA共聚物有潜力被开发成为一种通用载体，用于安全有效地递送其他基于核酸的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/557e6def5c02/polymers-12-00445-g008a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/c48c8672b2c3/polymers-12-00445-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/e19d82c93b8e/polymers-12-00445-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/0670f35734f6/polymers-12-00445-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/98ec6aae27e8/polymers-12-00445-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/1f6054f9e322/polymers-12-00445-g005a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/52c8b7362a49/polymers-12-00445-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/71ac569b266d/polymers-12-00445-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/557e6def5c02/polymers-12-00445-g008a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/c48c8672b2c3/polymers-12-00445-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/e19d82c93b8e/polymers-12-00445-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/0670f35734f6/polymers-12-00445-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/98ec6aae27e8/polymers-12-00445-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/1f6054f9e322/polymers-12-00445-g005a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/52c8b7362a49/polymers-12-00445-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/71ac569b266d/polymers-12-00445-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/062b/7077636/557e6def5c02/polymers-12-00445-g008a.jpg

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Integration of Polylactide into Polyethylenimine Facilitates the Safe and Effective Intracellular siRNA Delivery.

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引用本文的文献

[1]
Polyethylenimine Carriers for Drug and Gene Delivery.

Polymers (Basel). 2025-8-6

[2]
Advances in Nonviral mRNA Delivery Materials and Their Application as Vaccines for Melanoma Therapy.

ACS Appl Bio Mater. 2024-8-19

[3]
Progress in Delivery of siRNA-Based Therapeutics Employing Nano-Vehicles for Treatment of Prostate Cancer.

Bioengineering (Basel). 2020-8-10

本文引用的文献

[1]
Multivalency-assisted membrane-penetrating siRNA delivery sensitizes photothermal ablation via inhibition of tumor glycolysis metabolism.

Biomaterials. 2019-8-30

[2]
Promising approaches of small interfering RNAs (siRNAs) mediated cancer gene therapy.

Gene. 2019-8-24

[3]
Safe and efficient gene delivery based on rice bran polysaccharide.

Int J Biol Macromol. 2019-7-9

[4]
Polymeric Nanoparticles in Gene Therapy: New Avenues of Design and Optimization for Delivery Applications.

Polymers (Basel). 2019-4-25

[5]
Auto-fluorescent polymer nanotheranostics for self-monitoring of cancer therapy via triple-collaborative strategy.

Biomaterials. 2018-12-20

[6]
Polyethylenimine-based Formulations for Delivery of Oligonucleotides.

Curr Med Chem. 2019

[7]
Polyester based nanovehicles for siRNA delivery.

Mater Sci Eng C Mater Biol Appl. 2018-5-8

[8]
Histidine and arginine conjugated starch-PEI and its corresponding gold nanoparticles for gene delivery.

Int J Biol Macromol. 2018-8-29

[9]
Reversal of pancreatic desmoplasia by re-educating stellate cells with a tumour microenvironment-activated nanosystem.

Nat Commun. 2018-8-23

[10]
Smart polymeric nanoparticles with pH-responsive and PEG-detachable properties for co-delivering paclitaxel and survivin siRNA to enhance antitumor outcomes.

Int J Nanomedicine. 2018-4-20

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