Charge-Reversal Nano-Drug Delivery Systems in the Tumor Microenvironment: Mechanisms, Challenges, and Therapeutic Applications

The charge-reversal nano-drug delivery system (CRNDDS) is a promising system for delivering chemotherapy drugs and has gained widespread application in cancer treatment. In this review, we summarize the recent advancements in CRNDDSs in terms of cancer treatment. We also delve into the charge-reversal mechanism of the CRNDDSs, focusing on the acid-responsive, redox-responsive, and enzyme-responsive mechanisms. This study elucidates how these systems undergo charge transitions in response to specific microenvironmental stimuli commonly found in tumor tissues. Furthermore, this review explores the pivotal role of CRNDDSs in tumor diagnosis and treatment, and their potential limitations. By leveraging the unique physiological characteristics of tumors, such as the acidic pH, specific redox potential, and specific enzyme activity, these systems demonstrate enhanced accumulation and penetration at tumor sites, resulting in improved therapeutic efficacy and diagnostic accuracy. The implications of this review highlight the potential of charge-reversal drug delivery systems as a novel and targeted strategy for cancer therapy and diagnosis.