Bioinspired Copper Single‐Atom Catalysts for Tumor Parallel Catalytic Therapy

Abstract

The oxidation of intracellular biomolecules by reactive oxygen species (ROS) forms the basis for ROS‐based tumor therapy. However, the current therapeutic modalities cannot catalyze H2O2 and O2 concurrently for ROS generation, thereby leading to unsatisfactory therapeutic efficacy. Herein, it is reported a bioinspired hollow N‐doped carbon sphere doped with a single‐atom copper species (Cu‐HNCS) that can directly catalyze the decomposition of both oxygen and hydrogen peroxide to ROS, namely superoxide ion (O2•−) and the hydroxyl radical (•OH), respectively, in an acidic tumor microenvironment for the oxidation of intracellular biomolecules without external energy input, thus resulting in an enhanced tumor growth inhibitory effect. Notably, the Fenton reaction turnover frequency of Cu species in Cu‐HNCS is ≈5000 times higher than that of Fe in commercial Fe3O4 nanoparticles. Experimental results and density functional theory calculations reveal that the high catalytic activity of Cu‐HNCS originates from the single‐atom copper, and the calculation predicts a next‐generation Fenton catalyst. This work provides an effective paradigm of tumor parallel catalytic therapy for considerably enhanced therapeutic efficacy.

Single-Atom Catalysts for Biotherapy Applications: A Systematic Review

“…The deposition/coprecipitation strategy is also a common approach for SAC preparation, which was used to prepare carbon dot-supported atomically dispersed gold (MitoCAT-g), porphyrin-like single-atom Fe(III) metal-organic framework (P-MOF), and Pt/CeO 2 [ 23 , 24 , 25 ]. Apart from these two methods, SACs can be prepared via self-assembly, exemplified by OxgeMCC-r SAE, and multistep reactions, exemplified by N-doped carbon sphere doped with a single-atom copper species (Cu-HNCS) [ 26 , 27 ].…”

“…The active metal atoms of SACs included Fe, Zn, Co, Cu, Pt, Au, and Ru [ 15 , 17 , 18 , 19 , 20 , 22 , 23 , 24 , 25 , 26 , 27 ]. The selected support materials of the SACs included carbon materials, such as carbon nanoframes, carbon nanospheres, nitrogen-doped carbon, hollow nitrogen-doped carbon spheres, carbon dots, MOFs, Mn 3 [Co(CN 6 ) 6 ] 2 , and CeO 2 [ 15 , 17 , 18 , 19 , 20 , 21 , 23 , 24 , 25 , 26 , 27 ]. The structures of the included SACs are presented in Figure 1 .…”

“…Minimal cytotoxicity was reported in 1 remaining study. The cytocompatibility studies included a CCK8 assay [ 17 , 18 , 23 , 27 ] and/or Live/Dead assay [ 24 ] or an MTT assay [ 15 , 20 , 22 , 25 ] or a Cell Titer-Fluor assay [ 26 ], while studies conducted by Huo and coworkers [ 19 , 21 ] revealed the biocompatibilities of SAF NCs via the hematoxylin and eosin (HE) staining of major organs dissected from mice in different therapeutic groups. In regard to cytocompatibility, the single-atom catalyst of SAs/NC with bifunctional antioxidative enzymes for oxidative-stress cytoprotection exhibited the minimal cytotoxicity, which was reported by Ma and coworkers [ 15 ].…”

“…SACs were applied as a cancer therapy in five studies ( Table 1 ) [ 21 , 23 , 24 , 26 , 27 ]. These studies targeted breast cancer (four studies) and liver cancer (one study).…”

“…In addition, Gong et al found that carbon dot-supported atomically dispersed gold (MitoCAT-g) significantly suppressed tumor growth in subcutaneous and orthotopic patient-derived xenograft hepatocellular carcinoma models without adverse effects or toxicity, when compared with the saline contro1 ( Figure 2 f,g) [ 23 ]. Recently, a study conducted by Lu and coworkers reported that the bioinspired Cu-HNCS could generate two types of reactive oxygen species (ROS) (O 2 • − and •OH) through two parallel reactions, which significantly enhanced the efficacy of the parallel catalytic of tumors in in vitro and in vivo ( Figure 2 h–j) [ 27 ].…”