Charge shielding and targeted delivery strategies of cationic carriers

Cationic carriers have demonstrated broad application prospects in drug delivery due to their excellent drug-loading capacity and delivery performance. However, their high-density positive surface charge often leads to systemic toxicity and nonspecific uptake, posing significant barriers to clinical translation. In recent years, the emergence of charge shielding and stimuli-responsive strategies has provided effective avenues for modulating biocompatibility and targeting specificity. This review systematically summarizes the applications of chemical modification, natural polymer coating, and biomimetic membrane strategies in charge shielding. Furthermore, it explores the roles of endogenous stimuli such as pH, enzymes, and reactive oxygen species, as well as exogenous triggers like light and ultrasound, in achieving precise activation and controlled release. With the integration of multi-functional modules and the development of intelligent delivery platforms, cationic carriers are progressively advancing from laboratory research toward clinical translation. This review also discusses the translational potential and critical technical bottlenecks of related delivery systems, aiming to provide a theoretical framework and some reference for the design of next-generation smart delivery systems.