Construction and Application of a Technical Platform for Determining Cell Cycle- and Autophagy-Associated Cellular Uptake of Lipid-Based Nanoparticles

Cellular uptake of biomedical nanoparticles has been shown to be affected by key cellular biological properties. However, very little is known about the influence of cell cycle and autophagy on nanoparticle uptake. What’s even more tough is that several long-lasting methodological barriers hamper the experimental performance and restrict the research and development. Herein, a multi-functional platform was initially constructed for simultaneously overcoming existing obstacles by integrating several technical approaches, particularly mitotic shake-off, for complete and thorough cell cycle phase separation. Strikingly, further application of this platform revealed that G2-phase and M-phase cells, two cell populations previously muddled up together as G2/M-phase cells, respectively exhibited the maximum and minimum uptake of lipid-based nanoparticles. Moreover, our data generally provided a novel line of evidence for enhanced nanoparticle uptake by specific autophagy blockade. The cell cycle- and autophagy-associated characteristics of nanoparticle uptake discovered here offer new insights for optimization and application of nanomedicines. ### Competing Interest Statement The authors have declared no competing interest.