Department of Biomedical Science, College of Life Science, CHA University, 606-16 Yeoksam 1-dong, Kangnam-gu, Seoul 135-081, Republic of Korea.
Department of Molecular Science and Technology, Ajou University, San 5, Woncheon, Yeongtong, Suwon 443-749, Republic of Korea.
Biomaterials. 2014 May;35(16):4716-28. doi: 10.1016/j.biomaterials.2014.02.038. Epub 2014 Mar 13.
Specific genes and growth factors are involved in stem cell differentiation. In this study, we fabricated a delivery carrier for both protein and gene delivery that was introduced into human endothelial progenitor cells (EPCs). The highly negative charge carried by the heparin-modified pluronic nanogels allowed for binding to growth factors and localization in the core of nanogels. The residues of negatively charged heparin can complex with positively charged cationic materials, making it suitable for gene delivery. Supramolecular nanogels can be easily encapsulated the hydrophilic drugs and highly positive surfaces can be complexed with negative charge carrying plasmid DNA (pDNA). The size distribution, gel retardation, and denaturation of encapsulated growth factors and supramolecular nanogels modified with heparin were evaluated. The supramolecular nanogels containing basic fibroblast growth factors and complexing VEGF165 pDNA internalized into EPCs have been well formed vascular formation in matrigel gels. Proteins and genes introduced into EPCs using nanogels promoted neovascularization in an animal model of limb ischemia. EPCs that differentiated into endothelial cells both in vitro and in vivo were tested.
特定的基因和生长因子参与干细胞分化。在这项研究中，我们制备了一种既能输送蛋白质又能输送基因的载体，并将其导入人内皮祖细胞（EPC）中。肝素修饰的聚轮烷纳米凝胶所携带的高负电荷允许其与生长因子结合，并定位于纳米凝胶的核心。带负电荷的肝素残基可以与带正电荷的阳离子材料复合，使其适合于基因传递。超分子纳米凝胶可以很容易地包封亲水性药物，并且高度正的表面可以与带负电荷的质粒 DNA（pDNA）复合。评估了肝素修饰的超分子纳米凝胶对包封的生长因子的大小分布、凝胶阻滞和变性。含有碱性成纤维细胞生长因子的超分子纳米凝胶和复合 VEGF165 pDNA 的纳米凝胶已内化到 EPC 中，并在基质胶凝胶中形成了良好的血管形成。使用纳米凝胶将蛋白质和基因导入 EPC 中，促进了肢体缺血动物模型中的新血管生成。在体外和体内都检测到分化为内皮细胞的 EPC。
