Nanoparticle-enabled In Situ drug potency activation for enhanced tumor-specific therapy

Cancer treatment faces significant challenges including inadequate tumor specificity, drug resistance, and severe side effects, often resulting in unsatisfactory patient outcomes. Nanomedicines offer a transformative platform for tumor-targeted drug delivery and antitumor potency activation, providing an indispensable strategy for overcoming the severe damage to normal tissues caused by the inherent "always-on" cytotoxicity of conventional therapeutic agents. This review focuses on the emerging concept of "nanoparticle-enabled in situ drug potency activation", where inactive or minimally toxic agents are selectively activated within tumors to enhance the therapeutic efficacy and minimize the adverse effects. We systematically analyzed literature from PubMed and Web of Science databases spanning the last two decades, emphasizing experimental evidence supporting this in situ drug potency activation concept. Key strategies including stimuli-responsive prodrug nanoparticles, metal-induced activation, and bioorthogonal reactions are critically evaluated for their potential to overcome limitations in current cancer therapies. The findings highlight the potential of in situ potency activation as a promising alternative to conventional therapeutics, with far-reaching implications for advancing effective and safe cancer treatments.