Shi Changcan, Li Qian, Zhang Wencheng, Feng Yakai, Ren Xiangkui
School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, China.
Wenzhou Institute of Biomaterials and Engineering , Wenzhou 325011, China.
ACS Appl Mater Interfaces. 2015 Sep 16;7(36):20389-99. doi: 10.1021/acsami.5b06286. Epub 2015 Sep 3.
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.
在此,我们证明了REDV肽修饰的纳米颗粒(NPs)可作为一种活性靶向基因载体,用于凝聚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REDV肽的接枝修饰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活性靶向NPs。与带负电荷的pZNF580凝聚后,最终形成了REDV肽修饰的NPs/pZNF580复合物。由于特异性肽对ECs的结合亲和力,这些REDV肽修饰的NPs/pZNF580复合物在体外ECs与人动脉平滑肌细胞(SMCs)的共培养系统中能够被ECs特异性识别并黏附。在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%增加到34.8%。REDV肽偶联的NPs/pZNF580复合物对ECs的主动靶向特异性在共培养系统中仍然保留。本研究中的这些发现有助于开发用于人工血管内皮化的活性靶向基因载体。