Polymeric vectors are safer alternatives for gene delivery owing to their advantages as compared to viral vectors. To improve the stability and transfection efficiency of poly(lactic-co-glycolic acid) (PLGA)- and poly(ethylenimine) (PEI)-based vectors, poly(ethylene glycol) (PEG), folic acid (FA), arginylglycylaspartic acid (RGD) peptides and isoleucine-lysine-valine-alanine-valine (IKVAV) peptides were employed and PLGA–PEI–PEG–FA and PLGA–PEI–PEG–RGD copolymers were synthesized. PLGA–PEI–PEG–FA/DNA, PLGA–PEI–PEG–RGD/DNA and PLGA–PEI–PEG–RGD/IKVAV/DNA nanocomplexes (NCs) were formed through bulk mixing. The structure and properties, including morphology, particle size, surface charge and DNA encapsulation, of NCs were studied. Robust NCs with spherical shape, uniform size distribution and slightly positive charge were able to completely bind DNA above their respective N/P ratios. The critical N/P ratio for PLGA–PEI–PEG–FA/DNA, PLGA–PEI–PEG–RGD/DNA and PLGA–PEI–PEG–RGD/IKVAV/DNA NCs was identified to be 12:1, 8:1 and 10:1, respectively. The covalent modification of PEI through a combination of biodegradable PLGA, hydrophilic PEG and targeting motifs significantly decreased the cytotoxicity of PEI. The developed NCs showed both N/P ratio and cell type-dependent transfection efficiency. An increase in N/P ratio resulted in increased transfection efficiency, and much improved transfection efficiency of NCs was observed above their respective critical N/P ratios. This study provides a promising means to produce polymeric vectors for gene delivery.

与病毒载体相比，聚合载体具有优势，是基因递送的更安全的替代品。提高聚乳酸乙醇酸 (PLGA) 和聚氮丙啶 (PEI) 载体、聚乙二醇 (PEG)、叶酸 (FA)、精氨酰甘氨酰天冬氨酸的稳定性和转染效率使用（RGD）肽和异亮氨酸-赖氨酸-缬氨酸-丙氨酸-缬氨酸（IKVAV）肽，合成了PLGA-PEI-PEG-FA和PLGA-PEI-PEG-RGD共聚物。 PLGA–PEI–PEG–FA/DNA、PLGA–PEI–PEG–RGD/DNA 和 PLGA–PEI–PEG–RGD/IKVAV/DNA 纳米复合物 (NC) 通过批量混合形成。研究了NCs的结构和性质，包括形态、粒径、表面电荷和DNA封装。具有球形形状、均匀尺寸分布和轻微正电荷的坚固NC能够在高于其各自的N/P比率的情况下完全结合DNA。 PLGA–PEI–PEG–FA/DNA、PLGA–PEI–PEG–RGD/DNA 和 PLGA–PEI–PEG–RGD/IKVAV/DNA NC 的临界 N/P 比被确定为 12:1、8:1和 10:1。通过生物可降解的 PLGA、亲水性 PEG 和靶向基序的组合对 PEI 进行共价修饰，显着降低了 PEI 的细胞毒性。开发的 NC 显示 N/P 比和细胞类型依赖性转染效率。 N/P 比率的增加导致转染效率增加，并且观察到 NC 的转染效率大大提高，高于其各自的临界 N/P 比率。这项研究提供了一种生产用于基因传递的聚合载体的有前景的方法。