Qingdao Innovation and Development Base, Harbin Engineering University, Qingdao 266000, China.
College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001, China.
Nanoscale. 2024 Oct 10;16(39):18553-18569. doi: 10.1039/d4nr01853b.
Cooperative wrapping of nanoparticles (NPs) with small sizes is an important pathway for the uptake of NPs by cell membranes. However, the cooperative wrapping efficiency and the effects of NPs' rigidity remain ambiguous. With the aid of computer simulations, we show that the complete wrapping mechanism of cooperative endocytosis is that the aggregation of NPs leads to greater wrapping forces than the single NP case, which triggers the increase of the wrapping degree and in turn further increases the wrapping forces until they are finally fully taken up. The effects of the NP size, initial distance, interaction strength, arrangement and stiffness on cooperative endocytosis were systematically studied. The cooperative wrapping efficiency increases as the NP radius increases. Hexagonal close packed NPs have the highest internalization efficiency. When the interactions are strong, softer NPs exhibit higher endocytosis efficiency. We further propose two strategies by combining NPs with different wrapping properties for targeting applications. By combining two NPs decorated with different types of ligands, the combination NPs can only be fully endocytosed by the cell membrane with two cognate types of receptors and adhere to the normal cell membrane with only one type of receptor. We also design composite NPs using a large NP non-covalently decorated with several small NPs. By harnessing the competition between the ligand-receptor interactions and the excluded volume interactions between the small NPs and the lipid membrane, the composite NPs have targeting ability towards the cancer cell membrane. The design concept of combining NPs with different wrapping properties for drug targeting applications may be very promising in biomedicine.
纳米颗粒（NPs）的协同包裹是细胞膜摄取 NPs 的重要途径。然而，NPs 的协同包裹效率及其刚性的影响仍不明确。借助计算机模拟，我们表明协同胞吞作用的完整包裹机制是 NPs 聚集导致的包裹力大于单个 NP 的情况，这引发了包裹程度的增加，并进而进一步增加了包裹力，直到它们最终被完全摄取。系统研究了 NP 尺寸、初始距离、相互作用强度、排列和刚度对协同内吞作用的影响。随着 NP 半径的增加，协同包裹效率增加。六方密堆积的 NPs 具有最高的内化效率。当相互作用较强时，较软的 NPs 表现出更高的内吞效率。我们进一步提出了两种通过结合具有不同包裹特性的 NPs 用于靶向应用的策略。通过将两种用不同类型配体修饰的 NPs 结合在一起，组合 NPs 只能被具有两个同源受体的细胞膜完全内吞，并与只有一种受体的正常细胞膜结合。我们还使用一个大的 NP 非共价地修饰几个小的 NP 来设计复合 NP。通过利用配体-受体相互作用和小 NP 与脂质膜之间的排斥体积相互作用之间的竞争，复合 NPs 具有针对癌细胞膜的靶向能力。结合具有不同包裹特性的 NPs 用于药物靶向应用的设计概念在生物医学中可能非常有前途。
