Fig. 3.

Design guidelines of nuclear-targeted nanosystems. Small cargoes cross the nuclear envelope through passive diffusion, without interaction with NPC. Active targeting is necessary for large cargoes. NLS-cargoes interact with nuclear transport receptors to achieve large cargoes accumulation in the nucleus. Nuclear envelope permeability enhancement allows ROS and mechanical forces to enhance the permeability of the nuclear envelope, and thus facilitate large cargo nuclear transportation. Nuclear pore expansion is a direct manner that dexamethasone regulates to expand the size of NPC. INM inner nuclear membrane, ONM outer nuclear membrane, NPC nuclear pore complexes, NLS nuclear localization signal, Impα importin α, Impβ importin β, RanGTP Ran guanosine triphosphate