Biodegradation-Mediated Enzymatic Activity-Tunable Molybdenum Oxide Nanourchins for Tumor-Specific Cascade Catalytic Therapy

Recent advances in nanomedicine have facilitated the development of potent nanomaterials with intrinsic enzyme-like activities (nanozymes) for cancer therapy. However, it remains a great challenge to fabricate smart nanozymes that precisely perform enzymatic activity in tumor microenvironment without inducing off-target toxicity to surrounding normal tissues. Herein, we report on designed fabrication of biodegradation-medicated enzymatic activity-tunable molybdenum oxide nanourchins (MoO3–x NUs), which selectively perform therapeutic activity in tumor microenvironment via cascade catalytic reactions, while keeping normal tissues unharmed due to their responsive biodegradation in physiological environment. Specifically, the MoO3–x NUs first induce catalase (CAT)-like reactivity to decompose hydrogen peroxide (H2O2) in tumor microenvironment, producing a considerable amount of O2 for subsequent oxidase (OXD)-like reactivity of MoO3–x NUs; a substantial cytotoxic superoxide radical (·O2–) is thus generated for tumor cell apoptosis. Interestingly, once exposed to neutral blood or normal tissues, MoO3–x NUs rapidly lose the enzymatic activity via pH-responsive biodegradation and are excreted in urine, thus ultimately ensuring safety. The current study demonstrates a proof of concept of biodegradation-medicated in vivo catalytic activity-tunable nanozymes for tumor-specific cascade catalytic therapy with minimal off-target toxicity.