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用于基因递送的双膦酸钙/聚丙烯酸钙球体的合成

Synthesis of Calcium Bisphosphonate/Calcium Polyacrylate Spheres for Gene Delivery.

作者信息

Wei Xiaona, Liu Xiaodan, Wang Xue, Bao Yuanyuan, Shi Xin, Sun Liwei

机构信息

Institute of Chemistry for Functionalized Materials, School of Chemistry and Chemical Engineering, Liaoning Normal University, 850 Huanghe Road, Dalian 116029, China.

Jilin Technology Innovation Center for Chinese Medicine Biotechnology, College of Biology and Chemistry, Beihua University, 15 Jilin Street, Jilin 132013, China.

出版信息

ACS Omega. 2017 May 31;2(5):2017-2025. doi: 10.1021/acsomega.6b00437. Epub 2017 May 11.

DOI:10.1021/acsomega.6b00437
PMID:30023652
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6044815/
Abstract

Calcium bisphosphonate/calcium polyacrylate spheres were synthesized by a facile method and applied for the first time as gene vectors for transfection. The colloidal spheres of the PAA-Ca-HO complex, formed by sodium polyacrylate and calcium ions in the solution, were used as template to synthesize a spherical PAA-Ca-BPMP composite (CaBPMP/CaPAA) in the presence of 1,4-bis(phosphomethyl)piperazine (BPMP). The CaBPMP/CaPAA composite exhibits uniform and well-dispersed spheres with a particle size of about 200 nm as expected. The cytotoxicity assays confirm that CaBPMP/CaPAA spheres are quite safe for different cells even at a high concentration of 500 μg/mL. In vitro transfection results show that CaBPMP/CaPAA spheres serving as gene vectors are capable of transferring exogenous genes into different cells with about 25% of transfection efficiency and good reproducibility. The transfection capacity of CaBPMP/CaPAA spheres may be attributed to the controllable sphere morphology, low cytotoxicity, moderate DNA loading capacity, and bioresorbable property. The application of calcium phosphonates with adjustable surface properties derived from the different organic groups of phosphonic acid in gene delivery provides a new design idea for gene vectors.

摘要

通过一种简便的方法合成了双膦酸钙/聚丙烯酸钙球体，并首次将其用作转染的基因载体。由聚丙烯酸钠和溶液中的钙离子形成的PAA-Ca-HO复合物的胶体球体用作模板，在1,4-双（膦甲基）哌嗪（BPMP）存在下合成球形PAA-Ca-BPMP复合材料（CaBPMP/CaPAA）。如预期的那样，CaBPMP/CaPAA复合材料呈现出均匀且分散良好的球体，粒径约为200nm。细胞毒性试验证实，即使在500μg/mL的高浓度下，CaBPMP/CaPAA球体对不同细胞也相当安全。体外转染结果表明，作为基因载体的CaBPMP/CaPAA球体能够将外源基因导入不同细胞，转染效率约为25%，且具有良好的重复性。CaBPMP/CaPAA球体的转染能力可能归因于可控的球体形态、低细胞毒性、适度的DNA负载能力和生物可吸收性。源自膦酸不同有机基团的具有可调表面性质的膦酸钙在基因递送中的应用为基因载体提供了一种新的设计思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/c46ff2461e4e/ao-2016-00437y_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/eb351866709e/ao-2016-00437y_0010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/7671888a0ce4/ao-2016-00437y_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/66375057a010/ao-2016-00437y_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/0ec9ba507075/ao-2016-00437y_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/218d95b0de25/ao-2016-00437y_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/33928539efaa/ao-2016-00437y_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/c46ff2461e4e/ao-2016-00437y_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/eb351866709e/ao-2016-00437y_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/47f967739381/ao-2016-00437y_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/b433f5c0671f/ao-2016-00437y_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/7671888a0ce4/ao-2016-00437y_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/66375057a010/ao-2016-00437y_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/0ec9ba507075/ao-2016-00437y_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/218d95b0de25/ao-2016-00437y_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/33928539efaa/ao-2016-00437y_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acc8/6643382/c46ff2461e4e/ao-2016-00437y_0008.jpg

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