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核心技术专利：CN118964589B侵权必究
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优化生物相容性和基因传递效率的 DMAEA 和 DMAEAm：一种烟酸衍生共聚物方法。

Optimizing Biocompatibility and Gene Delivery with DMAEA and DMAEAm: A Niacin-Derived Copolymer Approach.

机构信息

Institute of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, Jena 07743, Germany.

Leibniz Institute on Aging-Fritz Lipmann Institute, Jena 07745, Germany.

出版信息

Biomacromolecules. 2024 Aug 12;25(8):4749-4761. doi: 10.1021/acs.biomac.4c00007. Epub 2024 Jul 4.

DOI:10.1021/acs.biomac.4c00007
PMID:38963401
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11323007/
Abstract

Gene therapy is pivotal in nanomedicine, offering a versatile approach to disease treatment. This study aims to achieve an optimal balance between biocompatibility and efficacy, which is a common challenge in the field. A copolymer library is synthesized, incorporating niacin-derived monomers 2-acrylamidoethyl nicotinate (AAEN) or 2-(acryloyloxy)ethyl nicotinate (AEN) with -(dimethylamino)ethyl acrylamide (DMAEAm) or hydrolysis-labile -(dimethylamino)ethyl acrylate (DMAEA). Evaluation of the polymers' cytotoxicity profiles reveals that an increase in AAEN or DMAEA molar ratios correlates with improved biocompatibility. Remarkably, an increase in AAEN in both DMAEA and DMAEAm copolymers demonstrated enhanced transfection efficiencies of plasmid DNA in HEK293T cells. Additionally, the top-performing polymers demonstrate promising gene expression in challenging-to-transfect cells (THP-1 and Jurkat cells) and show no significant effect on modulating immune response induction in treated murine monocytes. Overall, the best performing candidates exhibit an optimal balance between biocompatibility and efficacy, showcasing potential advancements in gene therapy.

摘要

基因治疗在纳米医学中具有重要作用，为疾病治疗提供了一种通用的方法。本研究旨在实现生物相容性和疗效之间的最佳平衡，这是该领域的一个共同挑战。合成了一个共聚物库，其中包含烟酸衍生单体 2-丙烯酰胺乙基烟酸（AAEN）或 2-（丙烯酰氧基）乙基烟酸（AEN）与-（二甲氨基）乙基丙烯酰胺（DMAEAm）或可水解的-（二甲氨基）乙基丙烯酸酯（DMAEA）。评估聚合物的细胞毒性谱表明，AAEN 或 DMAEA 摩尔比的增加与生物相容性的提高相关。值得注意的是，在 DMAEA 和 DMAEAm 共聚物中增加 AAEN 可提高质粒 DNA 在 HEK293T 细胞中的转染效率。此外，表现最佳的聚合物在难以转染的细胞（THP-1 和 Jurkat 细胞）中显示出有希望的基因表达，并且对调节经处理的小鼠单核细胞中免疫反应的诱导没有显著影响。总体而言，表现最佳的候选物在生物相容性和疗效之间表现出最佳的平衡，展示了基因治疗的潜在进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/54322ca9546c/bm4c00007_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/8675206dff80/bm4c00007_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/2fa96c1b879c/bm4c00007_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/c4b2991de119/bm4c00007_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/54d6f3a6b1fa/bm4c00007_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/f6fe42bf9f76/bm4c00007_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/168f5ea39781/bm4c00007_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/54322ca9546c/bm4c00007_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/8675206dff80/bm4c00007_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/2fa96c1b879c/bm4c00007_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/c4b2991de119/bm4c00007_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/54d6f3a6b1fa/bm4c00007_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/f6fe42bf9f76/bm4c00007_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/168f5ea39781/bm4c00007_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b1/11323007/54322ca9546c/bm4c00007_0007.jpg

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引用本文的文献

[1]
Comparing the transfection efficiency of cationic monomer ratios in vinylimidazole and aminoethyl methacrylate copolymers.

Int J Pharm X. 2025-3-4

[2]
- Challenges and Perspectives in Polyelectrolytes.

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本文引用的文献

[1]
Vitamin B3 Containing Polymers for Nanodelivery.

Macromol Biosci. 2024-7

[2]
Improving Gene Delivery: Synergy between Alkyl Chain Length and Lipoic Acid for PDMAEMA Hydrophobic Copolymers.

Macromol Rapid Commun. 2024-4

[3]
Optimization of Mixed Micelles Based on Oppositely Charged Block Copolymers by Machine Learning for Application in Gene Delivery.

Small. 2024-2

[4]
Gene therapy: Comprehensive overview and therapeutic applications.

Life Sci. 2022-4-1

[5]
The impact of anionic polymers on gene delivery: how composition and assembly help evading the toxicity-efficiency dilemma.

J Nanobiotechnology. 2021-9-27

[6]
Lipid nanoparticles for mRNA delivery.

Nat Rev Mater. 2021

[7]
Polymeric Delivery of Therapeutic Nucleic Acids.

Chem Rev. 2021-9-22

[8]
The Importance of Apparent pKa in the Development of Nanoparticles Encapsulating siRNA and mRNA.

Trends Pharmacol Sci. 2021-6

[9]
Improved gene delivery to K-562 leukemia cells by lipoic acid modified block copolymer micelles.

J Nanobiotechnology. 2021-3-6

[10]
Solely aqueous formulation of hydrophobic cationic polymers for efficient gene delivery.

Int J Pharm. 2021-1-25

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