Initiating localized catalytic chemical reactions in tumor microenvironment (TME) can achieve appealing tumor-therapeutic efficacy concurrently with high specificity and desirable biosafety, which is mainly dependent on the high performance of biomedical nanocatalysts. This report demonstrates that PEGylated single-atom Fe-containing nanocatalysts (PSAF NCs) could effectively trigger the in situ tumor-specific Fenton reaction to generate abundant toxic hydroxyl radicals (•OH) selectively under the acidic TME. Based on density functional theory, it has been theoretically uncovered that the nanocatalysts could specifically catalyze the heterogeneous Fenton reaction via a proton-mediated H2O2-homolytic pathway. These generated radicals could not only lead to the apoptotic cell death of malignant tumors, but also induce the accumulation of lipid peroxides, causing tumor cell ferroptosis, which synergistically lead to an impressive tumor suppression outcome. In the meantime, the favorable biodegradability and biocompatibility of PSAF NCs also guarantee their desirable biosafety both in vivo and in vitro.
Keywords: heterogeneous Fenton reaction; nanocatalytic medicine; photothermal effect; single-atom catalyst; tumor nanotherapy.