Morphological and mechanical determinants of cellular uptake of deformable nanoparticles

Understanding the interactions of nanoparticles (NPs) with cell membranes and regulating their cellular uptake processes are of fundamental importance to the design of drug delivery systems with minimum toxicity, high efficiency and long circulation time. Employing the procedure of coarse-graining, we built an elastically deformable NP model with tunable morphological and mechanical properties. We found that the cellular uptake of deformable NPs depends on their shape: an increase in the particle elasticity significantly slows the uptake rate of spherical NPs, slightly retards that of prolate NPs, and promotes the uptake of oblate NPs. The intrinsic mechanisms have been carefully investigated through analysis of the endocytic mechanisms and free energy calculations. These findings provide unique insights into how deformable NPs penetrate across cell membranes and offer novel possibilities for designing effective NP-based carriers for drug delivery.