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聚（β-氨基酯）的合成与表征以及用于高效基因递送的聚乙二醇化和非聚乙二醇化聚（β-氨基酯）/质粒DNA纳米颗粒的应用

Synthesis and Characterization of Poly (β-amino Ester) and Applied PEGylated and Non-PEGylated Poly (β-amino ester)/Plasmid DNA Nanoparticles for Efficient Gene Delivery.

作者信息

Iqbal Sajid, Martins Alessandro F, Sohail Muhammad, Zhao Jingjing, Deng Qi, Li Muhan, Zhao Zhongxi

机构信息

Department of Pharmaceutics, Key Laboratory of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

Laboratory of Materials, Macromolecules, and Composites (LaMMAC), Federal University of Technology - Paraná (UTFPR), Apucarana, Brazil.

出版信息

Front Pharmacol. 2022 Apr 8;13:854859. doi: 10.3389/fphar.2022.854859. eCollection 2022.

DOI:10.3389/fphar.2022.854859
PMID:35462891
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9023864/
Abstract

Polymer-based nanocarriers require extensive knowledge of their chemistries to learn functionalization strategies and understand the nature of interactions that they establish with biological entities. In this research, the poly (β-amino ester) (PβAE-447) was synthesized and characterized, aimed to identify the influence of some key parameters in the formulation process. Initially; PβAE-447 was characterized for aqueous solubility, swelling capacity, proton buffering ability, and cytotoxicity study before nanoparticles formulation. Interestingly, the polymer-supported higher cell viability than the Polyethylenimine (PEI) at 100 μg/ml. PβAE-447 complexed with GFP encoded plasmid DNA (pGFP) generated nanocarriers of 184 nm hydrodynamic radius (+7.42 mV Zeta potential) for cell transfection. Transfection assays performed with PEGylated and lyophilized PβAE-447/pDNA complexes on HEK-293, BEAS-2B, and A549 cell lines showed better transfection than PEI. The outcomes toward A549 cells (above 66%) showed the highest transfection efficiency compared to the other cell lines. Altogether, these results suggested that characterizing physicochemical properties pave the way to design a new generation of PβAE-447 for gene delivery.

摘要

基于聚合物的纳米载体需要深入了解其化学性质，以便学习功能化策略并理解它们与生物实体建立的相互作用的本质。在本研究中，合成并表征了聚（β-氨基酯）（PβAE-447），旨在确定配方过程中一些关键参数的影响。最初，在制备纳米颗粒之前，对PβAE-447进行了水溶性、溶胀能力、质子缓冲能力和细胞毒性研究。有趣的是，在100μg/ml时，该聚合物支持的细胞活力高于聚乙烯亚胺（PEI）。PβAE-447与绿色荧光蛋白编码质粒DNA（pGFP）复合，生成了用于细胞转染的流体动力学半径为184nm（ζ电位为+7.42mV）的纳米载体。用聚乙二醇化和冻干的PβAE-447/pDNA复合物对HEK-293、BEAS-2B和A549细胞系进行的转染试验显示，其转染效果优于PEI。与其他细胞系相比，对A549细胞的转染结果（高于66%）显示出最高的转染效率。总之，这些结果表明，表征物理化学性质为设计用于基因递送的新一代PβAE-447铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bcf/9023864/cb586de9213f/fphar-13-854859-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bcf/9023864/cb586de9213f/fphar-13-854859-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bcf/9023864/2326c82119bc/fphar-13-854859-g007.jpg
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