Macrophage-Targeting and Complete Lysosomal Degradation of Self-assembled Two-Dimensional Poly(ε-caprolactone) Platelet Particles

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 in vitro. 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.