Centre for Advanced Macromolecular Design, School of Chemistry, University of New South Wales, Sydney, New South Wales 2052, Australia.
Electron Microscope Unit, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, New South Wales 2052, Australia.
ACS Appl Mater Interfaces. 2022 Aug 10;14(31):35333-35343. doi: 10.1021/acsami.2c06555. Epub 2022 Jul 27.
Understanding cellular uptake and particle trafficking within the cells is essential for targeted drug delivery applications. Existing studies reveal that the geometrical aspects of nanocarriers, for example, shape and size, determine their cell uptake and sub-cellular transport pathways. However, considerable efforts have been directed toward understanding the cell uptake mechanism and trafficking of spherical particles. Detailed analysis on the uptake mechanism and downstream intracellular processing of non-spherical particles remains elusive. Here, we used polymeric two-dimensional platelets based on poly(ε-caprolactone) (PCL) prepared by living crystallization-driven self-assembly as a platform to investigate the cell uptake and intracellular transport of non-spherical particles . PCL is known to degrade only slowly, and these platelets were still stable after 2 days of incubation in artificial lysosomal media. Upon cell uptake, the platelets were transported through an endo/lysosomal pathway and were found to degrade completely in the lysosome at the end of the cell uptake cycle. We observed a morphological transformation of the lysosomes, which correlates with the stages of platelet degradation in the lysosome. Overall, we found an accelerated degradation of PCL, which was likely caused by mechanical forces inside the highly stretched endosomes.
了解细胞内的细胞摄取和颗粒转运对于靶向药物递送应用至关重要。现有研究表明，纳米载体的几何形状，例如形状和大小，决定了它们的细胞摄取和细胞内转运途径。然而，人们已经投入了相当大的努力来理解球形颗粒的细胞摄取机制和转运。对于非球形颗粒的摄取机制和下游细胞内处理的详细分析仍然难以捉摸。在这里，我们使用基于聚（ε-己内酯）（PCL）的聚合二维板作为平台，通过活的结晶驱动自组装制备，以研究非球形颗粒的细胞摄取和细胞内转运。PCL 已知降解速度较慢，这些板在人工溶酶体介质中孵育 2 天后仍保持稳定。在细胞摄取后，这些板通过内体/溶酶体途径运输，并在细胞摄取周期结束时在溶酶体中完全降解。我们观察到溶酶体的形态转变，这与溶酶体中血小板降解的阶段相关。总的来说，我们发现 PCL 的降解速度加快，这可能是由于高度拉伸的内体内部的机械力造成的。
