Oxygen Vacancy-Driven Reversible Free Radical Catalysis for Environment-Adaptive Cancer Chemodynamic Therapy

Amplifying free radical production by chemical dynamic catalysis to cause oxidative damage to cancer cells has received extensive interest for cancer-specific therapy. The major challenge is inevitable negative modulation on the tumor microenvironment (TME) by these species, hindering durable effectiveness. Here we show for the first time an oxygen vacancy-rich Bi-based regulator that allows environment-adaptive free radical catalysis. Specifically, the regulator catalyzes production of highly toxic O₂^.- and ^. OH in cancer cells via logic enzymatic reactions yet scavenges accumulation of free radicals and immunosuppressive mediators in TME-associated noncancerous cells. Atomic-level mechanistic studies reveal that such dual-modal regulating behavior is dominated by oxygen vacancies that well fit for free radical catalytic kinetics, along with distinguished cellular fates of this regulator. With this smart regulator, a "two birds with one shot" cancer dynamic therapy can be expected.