Institute of Genomics and Integrative Biology (CSIR), Delhi University Campus, Mall Road, Delhi 110007, India.
J Biomed Nanotechnol. 2009 Jun;5(3):264-77. doi: 10.1166/jbn.2009.1031.
Hyaluronic acid (HA)-polyethylenimine (PEI, 25 kDa) (HP) nanocomposites were fabricated for efficient targeting to solid tumors. Branched PEI was ionically blended with a natural mucopolysaccharide, HA, to partially block the positive charge and to impart site specificity to HP nanocomposites. A series of nanocomposites were prepared by varying the content of HA. HP nanocomposites were characterized by their size, morphology, zeta potential and evaluated for pDNA protection study, transfection efficiency and cytotoxicity. The competency of HP nanocomposites to relocate a plasmid encoding enhanced green fluorescent protein (pEGFP) gene was assessed in HEK293, HEK293T, and HeLa cells and found to be approximately 1-8 folds efficient compared to Superfect, Fugene, GenePORTER 2. HP nanocomposites also exhibited efficient transfection in serum-containing medium. MTT assay showed significantly improved cell viability in HEK293T, HepG2 and HeLa cells. The specificity of HP nanocomposites to target tumor was investigated in vivo by injecting pDNA-loaded HP-4 nanocomposite or PEI intravenously into mice bearing Ehrlich ascites tumor (EAT). The gamma scintigraphic studies showed a higher accumulation of HP-4 nanocomposite in the solid tumor compared to PEI. The results cumulatively advocate that HP nanocomposites could epitomize a viable alternative for site specific gene therapy.
透明质酸（HA）-聚乙烯亚胺（PEI，25 kDa）（HP）纳米复合材料被制备用于有效地靶向实体瘤。支化的 PEI 与天然粘多糖 HA 离子混合，部分中和正电荷并赋予 HP 纳米复合材料靶向性。通过改变 HA 的含量制备了一系列纳米复合材料。通过尺寸、形态、Zeta 电位对 HP 纳米复合材料进行了表征，并对其 pDNA 保护研究、转染效率和细胞毒性进行了评价。评估了 HP 纳米复合材料在 HEK293、HEK293T 和 HeLa 细胞中重新定位编码增强型绿色荧光蛋白（pEGFP）基因的质粒的能力，与 Superfect、Fugene 和 GenePORTER 2 相比，其效率约为 1-8 倍。HP 纳米复合材料在含血清的培养基中也表现出高效的转染。MTT 测定表明，在 HEK293T、HepG2 和 HeLa 细胞中细胞活力显著提高。通过向患有艾氏腹水瘤（EAT）的小鼠静脉注射 pDNA 负载的 HP-4 纳米复合材料或 PEI，体内研究了 HP 纳米复合材料靶向肿瘤的特异性。γ闪烁显像研究表明，与 PEI 相比，HP-4 纳米复合材料在实体瘤中的积累更高。这些结果综合表明，HP 纳米复合材料可以作为一种可行的靶向基因治疗替代方案。
