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蛋白水解酶沙雷肽酶与阳离子嵌段共聚物胶束的纳米复合物可增强人类细胞的增殖和迁移能力。

Nanosized Complexes of the Proteolytic Enzyme Serratiopeptidase with Cationic Block Copolymer Micelles Enhance the Proliferation and Migration of Human Cells.

作者信息

Kamenova Katya, Prancheva Anna, Radeva Lyubomira, Yoncheva Krassimira, Zaharieva Maya M, Najdenski Hristo M, Petrov Petar D

机构信息

Institute of Polymers, Bulgarian Academy of Sciences, bl.103 Akad. G. Bonchev Str., 1113 Sofia, Bulgaria.

Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.

出版信息

Pharmaceutics. 2024 Jul 25;16(8):988. doi: 10.3390/pharmaceutics16080988.

Abstract

In this study, we describe the preparation of the cationic block copolymer nanocarriers of the proteolytic enzyme serratiopeptidase (SER). Firstly, an amphiphilic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA-b-PCL-b-PDMAEMA) triblock copolymer was synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization. Then, cationic micellar nanocarriers consisting of a PCL hydrophobic core and a PDMAEMA hydrophilic shell were formed by the solvent evaporation method. SER was loaded into the polymeric micelles by electrostatic interaction between the positively charged micellar shell and the negatively charged enzyme molecules. The particle size, zeta potential, and colloid stability of complexes as a function of SER concentration were investigated by dynamic and electrophoretic light scattering. It was found that SER retained its proteolytic activity after immobilization in polymeric carriers. Moreover, the complexes have a concentration-dependent enhancing effect on the proliferation and migration of human keratinocyte HaCaT and gingival fibroblast HGF cells.

摘要

在本研究中,我们描述了蛋白水解酶沙雷肽酶(SER)阳离子嵌段共聚物纳米载体的制备。首先,通过可逆加成-断裂链转移(RAFT)聚合反应合成了两亲性聚甲基丙烯酸2-(二甲氨基)乙酯-b-聚(ε-己内酯)-b-聚甲基丙烯酸2-(二甲氨基)乙酯(PDMAEMA-b-PCL-b-PDMAEMA)三嵌段共聚物。然后,采用溶剂蒸发法形成了由PCL疏水核和PDMAEMA亲水壳组成的阳离子胶束纳米载体。通过带正电的胶束壳与带负电的酶分子之间的静电相互作用,将SER载入聚合物胶束中。通过动态光散射和电泳光散射研究了复合物的粒径、ζ电位和胶体稳定性随SER浓度的变化。结果发现,SER固定在聚合物载体中后仍保留其蛋白水解活性。此外,这些复合物对人角质形成细胞HaCaT和牙龈成纤维细胞HGF细胞的增殖和迁移具有浓度依赖性增强作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9867/11358905/e51a0c26192f/pharmaceutics-16-00988-g001.jpg

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