Charge-reversal nanomedicines as a smart bullet for deep tumor penetration

Complex composition and abnormal growth state of cells and tissues in the solid tumor microenvironment often lead to high density and stiffness different from normal tissues, thus forming a solid physical barrier to prevent the penetration of nanomedicines. Charge-reversal nanomedicines are a kind of emerging smart nano-systems that can show a change of surface charge from negative to positive before and after reaching the tumor site, thus effectively enhancing tumor penetration by promoting transcytosis, while maintaining a high in vivo safety. In this review, we provide a detailed summary of the current classification of charge-reversal nanomaterials and their working mechanisms, as well as also comment on the prospects and challenges of the smart nano-systems in the direction of thoroughly solving the tumor penetration problem.