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REDV Peptide Conjugated Nanoparticles/pZNF580 Complexes for Actively Targeting Human Vascular Endothelial Cells

机译:REDV肽共轭纳米粒子/ pZNF580复合物主动靶向人类血管内皮细胞

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摘要

Herein, we demonstrate that the REDV peptide modified nanoparticles (NPs) can serve as a kind of active targeting gene carrier to condensate pZNF580 for specific promotion of the proliferation of endothelial cells (ECs). First, we synthesized a series of biodegradable amphiphilic copolymers by ring-opening polymerization reaction and graft modification with REDV peptide. Second, we prepared active targeting NPs via self-assembly of the amphiphilic copolymers using nanoprecipitation technology. After condensation with negatively charged pZNF580, the REDV peptide modified NPs/pZNF580 complexes were formed finally. Due to the binding affinity toward ECs of the specific peptide, these REDV peptide modified NPs/pZNF580 complexes could be recognized and adhered specifically by ECs in the coculture system of ECs and human artery smooth muscle cells (SMCs) in vitro. After expression of ZNF580, as the key protein to promote the proliferation of ECs, the relative ZNF580 protein level increased from 15.7% to 34.8%. The specificity in actively targeting ECs of the REDV peptide conjugated NPs/pZNF580 complexes was still retained in the coculture system. These findings in the present study could facilitate the development of actively targeting gene carriers for the endothelialization of artificial blood vessels.
机译:在本文中,我们证明了REDV肽修饰的纳米粒子(NPs)可以作为一种有效的靶向基因载体来浓缩pZNF580,以特异性促进内皮细胞(ECs)的增殖。首先,我们通过开环聚合反应和用REDV肽接枝改性,合成了一系列可生物降解的两亲共聚物。其次,我们使用纳米沉淀技术通过两亲共聚物的自组装制备了主动靶向的NP。与带负电荷的pZNF580缩合后,最终形成REDV肽修饰的NPs / pZNF580复合物。由于特定肽对EC的结合亲和力,这些REDV肽修饰的NPs / pZNF580复合物可以在EC和人动脉平滑肌细胞(SMC)的共培养系统中被EC特异性识别并粘附。 ZNF580表达后,作为促进ECs增殖的关键蛋白,相对ZNF580蛋白水平从15.7%提高到34.8%。在共培养系统中仍保留了主动靶向REDV肽缀合的NPs / pZNF580复合物的EC的特异性。本研究中的这些发现可以促进针对人工血管内皮化的主动靶向基因载体的开发。

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