Charge‐Reversible Nanoparticles: Advanced Delivery Systems for Therapy and Diagnosis

The past two decades have witnessed a rapid progress in the development of surface charge‐reversible nanoparticles (NPs) for drug delivery and diagnosis. These NPs are able to elegantly address the polycation dilemma. Converting their surface charge from negative/neutral to positive at the target site, they can substantially improve delivery of drugs and diagnostic agents. By specific stimuli like a shift in pH and redox potential, enzymes, or exogenous stimuli such as light or heat, charge reversal of NP surface can be achieved at the target site. The activated positive surface charge enhances the adhesion of NPs to target cells and facilitates cellular uptake, endosomal escape, and mitochondrial targeting. Because of these properties, the efficacy of incorporated drugs as well as the sensitivity of diagnostic agents can be essentially enhanced. Furthermore, charge‐reversible NPs are shown to overcome the biofilm formed by pathogenic bacteria and to shuttle antibiotics directly to the cell membrane of these microorganisms. In this review, the up‐to‐date design of charge‐reversible NPs and their emerging applications in drug delivery and diagnosis are highlighted. Charge‐reversible nanoparticles are drug delivery systems that change their surface charge in response to specific stimuli like the pH, redox‐conditions, enzymes, exogenous stimuli, or a combination of them. This charge reversion from negative to positive enhances cellular uptake and targeted release of the payloads, promising more effective and precise treatments for various diseases.