Abstract
The rational construction of efficient hypoxia-tolerant nanocatalysts capable of generating singlet oxygen ((1)O(2)) without external stimuli is of great importance for tumor therapy. Herein, uniformly dispersed and favorable biosafety profile graphitic carbon nitride quantum dots immobilized with Fe-N(4) moieties modulated by axial O atom (denoted as O-Fe-N(4)) are developed for converting H(2)O(2) into (1)O(2) via Russell reaction, without introducing external energy. Notably, O-Fe-N(4) performs two interconnected catalytic properties: glutathione oxidase-mimic activity to provide substrate for subsequent (1)O(2) generation, avoiding the blunting anticancer efficacy by glutathione. The O-Fe-N(4) catalyst demonstrates a specific activity of 79.58 U mg(-1) at pH 6.2, outperforming the most reported Fe-N(4) catalysts. Density functional theory calculations demonstrate that the axial O atom can effectively modulate the relative position and electron affinity between Fe and N, lowering the activation energy, strengthening the selectivity, and thus facilitating the Russell-type reaction. The gratifying enzymatic activity stemming from the well-defined Fe-N/O structure can inhibit tumor proliferation by efficiently downregulating glutathione peroxidase 4 activity and inducing lipid peroxidation. Altogether, the O-Fe-N(4) catalyst not only represents an efficient platform for self-cascaded catalysis to address the limitations of (1)O(2)-involved cancer treatment but also provides a paradigm to enhance the performance of the Fe-N(4) catalyst.