Regulating cellular uptake pathways using engineered materials is becoming a vital strategy for efficient gene transfer because the success of gene delivery most often relies on the uptake mechanism and the intracellular fate of the delivery vectors. The uptake of gene carriers can be greatly affected by the various physical, geometrical, chemical, and biological characteristics of the delivery vectors. In the design of gene delivery materials, it is important to understand not only how gene carriers are taken up and transported into cells, but also how the uptake mechanism can be regulated. In this review, we discuss polymeric materials that regulate cellular uptake pathways for highly effective delivery of gene therapeutics, elucidate various routes of cellular uptake that alter the intracellular fate of polymeric gene carriers and finding efficient strategies for overcoming extracellular and intracellular obstacles. We also discuss the structures of polymeric materials in order to understand how they regulate cellular uptake. Lastly, we discuss various strategic approaches, including essential cues on how to regulate the cellular uptake pathways of polymeric carriers and how to control their endocytic trafficking to improve the efficacy of gene delivery.

使用工程材料调节细胞摄取途径正在成为有效基因转移的重要策略，因为基因递送的成功通常依赖于递送载体的摄取机制和细胞内命运。基因载体的摄取会受到递送载体的各种物理、几何、化学和生物学特性的极大影响。在基因传递材料的设计中，重要的是不仅要了解基因载体是如何被摄取和转运到细胞中的，而且还要了解如何调节摄取机制。在这篇综述中，我们讨论了调节细胞摄取途径以高效传递基因治疗的聚合物材料，阐明改变聚合基因载体细胞内命运的各种细胞摄取途径，并找到克服细胞外和细胞内障碍的有效策略。我们还讨论了聚合物材料的结构，以了解它们如何调节细胞摄取。最后，我们讨论了各种战略方法，包括如何调节聚合载体的细胞摄取途径以及如何控制其内吞运输以提高基因传递效率的基本线索。