The developing nanoparticle therapeutic agents triggered by tumor microenvironment are a feasible strategy for the substantial elevation of accuracy of diagnosis and the reduction of side effects in cancer treatments. Dysregulated H2S production from the enzyme system of overexpressed cystathionine β-synthase has long been considered to act as an autocrine and paracrine factor for the tumor growth and proliferation of colon cancer. Herein, for the first time, an endogenous H2S-activated copper metal–organic framework (Cu-MOF; HKUST-1) nanoenzyme has been demonstrated to synergistically mediate H2S-activated near-infrared photothermal therapy and chemodynamic therapy in the effective treatment of colon cancer. This endogenous biomarker-triggered “turn-on” strategy to generate therapeutic agents in situ could largely simplify the constitution of nanomedicine by avoiding the cargo introduction and thus supply great promise for the precise treatments of colon cancer.

The increasing resistance risks of conventional antibiotic abuse and the formed biofilm on the surface of wounds have been demonstrated to be the main problems for bacteria‐caused infections and unsuccessful wound healing. Treatment by reactive oxygen species, such as the commercial H2O2, is a feasible way to solve those problems, but limits in its lower efficiency. Herein, an ionic covalent‐organic framework‐based nanozyme (GFeF) with self‐promoting antibacterial effect and good biocompatibility has been developed as glucose‐triggered cascade catalyst against bacterial wound infection. Besides the efficient conversion of glucose to hydrogen peroxide, the produced gluconic acid by loading glucose oxidase can supply a compatible catalytic environment to substantially improve the peroxidase activity for generating more toxic hydroxyl radicals. Meanwhile, the adhesion between the positively charged GFeF and the bacterial membrane can greatly enhance the healing effects. This glucose‐triggered cascade strategy can reduce the harmful side effects by indirectly producing H2O2, potentially used in the wound healing of diabetic patients.