Reversible Chemistry for Cancer Therapy and Diagnosis

Reversible chemistry strategies in cancer treatment and diagnosis have attracted significant attention due to their unique ability to dynamically respond to both exogenous (e.g., light, ultrasound, and magnetic fields) and endogenous (e.g., pH, redox potential, and hypoxia-normoxia) stimuli, thereby modulating the functional characteristics of materials. Reversible cancer therapy offers distinct advantages over irreversible cancer therapy including sustainable cyclic function, shape-specific function, tumor-site-specific function, tumor-specific targeting, on-demand control, deep tumor penetration, and long-term circulation and drug retention. This review comprehensively explores reversible chemistry strategies for cancer therapy and imaging, providing a comprehensive overview of utilizing multiscale (molecular-scale, nanoscale, microscale, and macroscale) materials for various reversible control mechanisms, such as electronic transitions, molecular isomerization, valence state changes, material morphology changes, and mechanical motion. Furthermore, we present various applications, advantages, and challenges of reversible chemistry in cancer therapy and imaging along with the potential for clinical applications and associated challenges. In conclusion, reversible therapeutic and diagnostic approaches offer promising avenues for precise cancer treatment and early diagnosis.