The clinical treatment efficacies of nanomedicines are commly burdened with two main challenges of inefficient tumor tissue penetration and cellular uptake owing to their poor tissue and biomembrane permeability[1].To overcome the above drawbacks,a size-shrinkable and charge-reversible multi-adaptive nanoassembly (i.e.,mAdaNA) was prepared for smart drug delivery,especially for enhanced tissue penetration and cellular uptake (Fig.1).