An All-in-One Bioorthogonal System for Precise Cancer Therapy

Bioorthogonal chemistry exhibits great potential in drug design and synthesis. However, the usage of two components (prodrug and trigger) is still an urgent conundrum, which are separated from each other and then delivered to the organism individually. Herein, for the first time, we designed and constructed an innovative all-in-one nanoplatform integrating the prodrug and bioorthogonal catalyst for precise therapy. Notably, the prodrug and catalyst are first segregated from each other with a CaCO3-mineralized shell before entering pathological conditions. Having arrived at the tumor sites, the prodrug would be able to access the bioorthogonal catalyst following the collapse of CaCO3, which enables in situ localized drug synthesis. The system was further characterized in tumor-bearing mice with excellent anticancer efficiency. This is of great value in bioorthogonal chemistry-based cancer therapy.