Bioorthogonal Chemistry-Based Prodrug Strategies for Enhanced Biosafety in Tumor Treatments: Current Progress and Challenges

Abstract

Cancer is a major global health concern, and while chemotherapy remains a common treatment, its non-specific toxicity and widespread distribution can cause systemic side effects and limit effectiveness against tumors. Developing safer chemotherapy options is crucial. Prodrugs offer promise by staying inactive until they reach the cancer site, where they are activated by enzymes or specific factors, reducing side effects and improving targeting. However, the subtle differences in the microenvironment between tumor and normal tissues could still result in unintended cytotoxicity. Bioorthogonal reactions, prized for their selectivity and precision without interfering with natural biochemical processes, are gaining popularity. By integrating these reactions with prodrug strategies, there’s potential to develop potent chemotherapy drugs. This review explores the safety and effectiveness of prodrug strategies using various bioorthogonal reactions in tumor treatments.