Hao Xuefang, Li Qian, Wang Huaning, Muhammad Khan, Guo Jintang, Ren Xiangkui, Shi Changcan, Xia Shihai, Zhang Wencheng, Feng Yakai
School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Tianjin 300350, China.
Collaborative Innovation Center of Chemical Science and Chemical Engineering (Tianjin), Tianjin 300350, China.
ACS Biomater Sci Eng. 2018 Aug 13;4(8):2870-2878. doi: 10.1021/acsbiomaterials.8b00529. Epub 2018 Jul 3.
Recently, polymeric micelles with different biodegradable hydrophobic cores, such as poly(lactide--glycolide) (PLGA) and poly(lactide--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 W 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 W modified gene complexes was higher than the complexes without W target function. A similar trend was also found in transfection tests in vitro, which further demonstrated the effect of W 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 W 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 W modification.
最近，具有不同可生物降解疏水核心的聚合物胶束，如聚（丙交酯-乙交酯）（PLGA）和聚（丙交酯-3(S)-甲基-吗啉-2,5-二酮）（PLMD），已被用于基因递送。可生物降解的疏水核心在基因递送中应发挥重要作用。然而，很少有研究专注于通过改变聚合物胶束的疏水核心来选择性促进内皮细胞（ECs）的增殖和迁移以及血管生成。在此，我们分别制备了两种以PLGA和PLMD为疏水核心、聚乙二醇（PEG）和聚乙烯亚胺（PEI）为混合亲水壳的W肽（对ECs有选择性粘附作用）修饰的胶束。琼脂糖凝胶电泳分析证明了它们凝聚pEGFP-ZNF580（pZNF580）形成基因复合物的能力。MTT结果表明，以PLMD为核心的胶束的相对细胞活力高于对照组和以PLGA为核心的胶束。这些W修饰的基因复合物的细胞摄取能力高于没有W靶向功能的复合物。在体外转染试验中也发现了类似的趋势，这进一步证明了W肽和不同疏水核心对基因递送的影响。用PLGA核心的基因复合物处理的迁移细胞数量在非靶向组为82，靶向组为；而用PLMD核心的复合物在非靶向组为88，靶向组为120。以PLMD为核心的W肽修饰复合物的类毛细血管形成比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W修饰可以提高转染效率、促进细胞增殖、迁移和血管生成。
