Charge reversal nano-systems for tumor therapy

Abstract Surface charge of biological and medical nanocarriers has been demonstrated to play an important role in cellular uptake. Owing to the unique physicochemical properties, charge-reversal delivery strategy has rapidly developed as a promising approach for drug delivery application, especially for cancer treatment. Charge-reversal nanocarriers are neutral/negatively charged at physiological conditions while could be triggered to positively charged by specific stimuli (i.e., pH, redox, ROS, enzyme, light or temperature) to achieve the prolonged blood circulation and enhanced tumor cellular uptake, thus to potentiate the antitumor effects of delivered therapeutic agents. In this review, we comprehensively summarized the recent advances of charge-reversal nanocarriers, including: (i) the effect of surface charge on cellular uptake; (ii) charge-conversion mechanisms responding to several specific stimuli; (iii) relation between the chemical structure and charge reversal activity; and (iv) polymeric materials that are commonly applied in the charge-reversal delivery systems. Graphical Abstract