Construction and application of a technical platform for determining cell cycle- and autophagy-associated cellular accumulation of lipid-based nanoparticles

Cellular accumulation of biomedical nanoparticles could be affected by cellular biological properties. However, little is known about the influence of cell cycle and autophagy on nanoparticle accumulation. What’s even more tough is that several long-lasting methodological barriers have hampered the experimental performance and restricted related research progress. Herein, a multi-functional platform was constructed for simultaneously overcoming existing obstacles by integrating several technical approaches, particularly mitotic shake-off, for thorough cell cycle phase separation. Strikingly, 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 accumulation of lipid-based nanoparticles. Moreover, although further verification is needed, we have provided a novel line of evidence for enhanced nanoparticle accumulation by autophagy blockade. Besides providing a technical solution, this study discovered characteristic cell cycle- and autophagy-associated nanoparticle accumulations that may offer new insights for optimization and application of nanomedicines.