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CAGW Modified Polymeric Micelles with Different Hydrophobic Cores for Efficient Gene Delivery and Capillary-like Tube Formation
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2018-06-19 00:00:00 , DOI: 10.1021/acsbiomaterials.8b00529
Xuefang Hao 1 , Qian Li 1 , Huaning Wang 1 , Khan Muhammad 1 , Jintang Guo 1, 2 , Xiangkui Ren 1, 2, 3 , Changcan Shi 4, 5 , Shihai Xia 6 , Wencheng Zhang 7 , Yakai Feng 1, 2, 3
Affiliation  

Recently, polymeric micelles with different biodegradable hydrophobic cores, such as poly(lactide-co-glycolide) (PLGA) and poly(lactide-co-3(S)-methyl-morpholine-2,5-dione) (PLMD), have been used for gene delivery. The biodegradable hydrophobic cores should play an important role in gene delivery. However, little research has focused on selectively promoting proliferation and migration of endothelial cells (ECs) as well as vascularization by altering hydrophobic cores of polymeric micelles. Herein, we prepared two kinds of CAGW peptide (selective adhesion for ECs) modified micelles with PLGA and PLMD as hydrophobic cores, respectively, and poly(ethylene glycol) (PEG) and polyethylenimine (PEI) as mixed hydrophilic shell. Their ability of condensing pEGFP-ZNF580 (pZNF580) to form gene complexes was proved by agarose gel electrophoresis assay. MTT results showed that the relative cell viability of the micelles with PLMD cores was higher than control groups and the micelles with PLGA cores. The cellular uptake ability of these CAGW modified gene complexes was higher than the complexes without CAGW target function. A similar trend was also found in transfection tests in vitro, which further demonstrated the effect of CAGW peptide and different hydrophobic cores on gene delivery. The number of migrated cells treated by the gene complexes with PLGA cores was 82 (nontarget group) and 115 (target group), whereas the complexes with PLMD cores was 88 (nontarget group) and 120 (target group). Capillary-like tube formation of CAGW peptide modified complexes with PLMD core group was much higher (about 6 times) than the PEI(10 kDa)/pZNF580 group. These results demonstrated that transfection efficiency, cell proliferation, migration, and vascularization could be promoted by altering hydrophobic cores and CAGW modification.

中文翻译:

CAG W修饰的具有不同疏水核心的聚合物胶束,用于有效的基因传递和毛细管样管形成

近年来,随着不同的生物可降解的疏水性芯,例如聚(丙交酯-聚合物胶束-glycolide)(PLGA)和聚(丙交酯--3(S) -甲基吗啉-2,5-二酮)(PLMD),具有用于基因传递。可生物降解的疏水核心应在基因传递中起重要作用。然而,很少有研究集中在通过改变聚合物胶束的疏水核心来选择性地促进内皮细胞(EC)的增殖和迁移以及血管形成。在这里,我们准备了两种CAGW肽(对EC的选择性粘附)修饰的胶束,分别具有PLGA和PLMD作为疏水核,而聚乙二醇(PEG)和聚乙烯亚胺(PEI)作为混合亲水壳。通过琼脂糖凝胶电泳分析证明了它们具有冷凝pEGFP-ZNF580(pZNF580)形成基因复合物的能力。MTT结果表明,具有PLMD核心的胶束的相对细胞活力高于对照组和具有PLGA核心的胶束。这些CAG W修饰的基因复合物的细胞摄取能力高于没有CAG W靶功能的复合物。在体外转染测试中也发现了类似的趋势,这进一步证明了CAG的作用W肽和基因传递中的不同疏水核心。用具有PLGA核心的基因复合物处理的迁移细胞数为82(非目标组)和115(目标组),而具有PLMD核心的复合物处理的细胞数为88(非目标组)和120(目标组)。具有PLMD核心组的CAG W肽修饰的复合物的毛细管样管形成要比PEI(10 kDa)/ pZNF580组高得多(约6倍)。这些结果表明,通过改变疏水核心和CAG W修饰可以提高转染效率,细胞增殖,迁移和血管形成。
更新日期:2018-06-19
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