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Abstract 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 O 2 .− 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.
Yuan et al. (Thu,) studied this question.