State Key Laboratory of Tree Genetics and Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China.
Key Laboratory of Genetics and Breeding in Forest Trees and Ornamental Plants, Ministry of Education, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China.
Int J Mol Sci. 2024 Jun 21;25(13):6826. doi: 10.3390/ijms25136826.
The surface functionalization of polymer-mediated drug/gene delivery holds immense potential for disease therapy. However, the design principles underlying the surface functionalization of polymers remain elusive. In this study, we employed computer simulations to demonstrate how the stiffness, length, density, and distribution of polymer ligands influence their penetration ability across the cell membrane. Our simulations revealed that the stiffness of polymer ligands affects their ability to transport cargo across the membrane. Increasing the stiffness of polymer ligands can promote their delivery across the membrane, particularly for larger cargoes. Furthermore, appropriately increasing the length of polymer ligands can be more conducive to assisting cargo to enter the lower layer of the membrane. Additionally, the distribution of polymer ligands on the surface of the cargo also plays a crucial role in its transport. Specifically, the one-fourth mode and stripy mode distributions of polymer ligands exhibited higher penetration ability, assisting cargoes in penetrating the membrane. These findings provide biomimetic inspiration for designing high-efficiency functionalization polymer ligands for drug/gene delivery.
聚合物介导的药物/基因传递的表面功能化在疾病治疗方面具有巨大的潜力。然而，聚合物表面功能化的设计原则仍然难以捉摸。在这项研究中，我们使用计算机模拟来演示聚合物配体的刚度、长度、密度和分布如何影响它们穿过细胞膜的穿透能力。我们的模拟表明，聚合物配体的刚度会影响其运输货物穿过膜的能力。增加聚合物配体的刚度可以促进它们穿过膜的输送，特别是对于较大的货物。此外，适当增加聚合物配体的长度可以更有利于辅助货物进入膜的下层。此外，货物表面上聚合物配体的分布在其运输中也起着至关重要的作用。具体来说，聚合物配体的四分之一模式和条纹模式分布表现出更高的穿透能力，有助于货物穿透膜。这些发现为设计高效的药物/基因传递功能化聚合物配体提供了仿生学启示。
