Metals Advances ›› 2026, Vol. 41: 1-15.DOI: 10.1016/j.metadv.2026.02.008
• Review Article • Next Articles
Yongfeng Sua,b,1, Fei Yanga,1, Han Lina,c, Jian Hana,b, Junda Lua,b, Jianwen Chenga,b,*(
)
Received:2025-10-31
Revised:2026-01-01
Accepted:2026-01-09
Online:2026-03-10
Published:2026-02-07
Contact:
*Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China. E-mail address: About author:1These authors contributed equally to this work.
Yongfeng Su, Fei Yang, Han Lin, Jian Han, Junda Lu, Jianwen Cheng. Advances in metal-hybridized nanoenzymes for catalytic cancer diagnosis and therapy[J]. Metals Advances, 2026, 41: 1-15.
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| Nanozyme | Activity | Substrate | Method | Application | Ref. |
|---|---|---|---|---|---|
| PW12@ZIF-67-Au | OXD | TMB | Colorimetry and electrochemistry | AFP detection | [ |
| i3k@Au/Cu | POD | TMB and H2O2 | Electrochemistry | CEA detection | [ |
| Cu2-xAgxS@liposome | POD | TMB and H2O2 | Colorimetry and fluorometry | CEA detection | [ |
| R-CQDs@Fe-NC | OXD | TMB | Colorimetry and fluorometry | PSA detection | [ |
| Mn3O4/Pd@Pt/HRP | HRP | H2O2 | Colorimetric immunoassay | HER2 detection | [ |
| AgNPs@GQDs-GOx | GOx and POD | Glucose | Bioimaging | Diagnosis and therapy | [ |
| Fe3O4@SiO2-APTES-NH2@Cyt-Cyt@FA | POD | H2O2 | Bioimaging and colorimetry | Diagnosis | [ |
| ZnMnFe2O4-PEG-FA | POD | H2O2 | PAI and MRI | Diagnosis and therapy | [ |
| Ang-IR780-MnO2-PLGA | GPx | GSH | PAI and FLI | Diagnosis and therapy | [ |
| IR808/DOX@Psome/MnO2 | POD | H2O2 | MRI and FLI | Diagnosis and therapy | [ |
| CPT/DM-FA | GPx and OXD | GSH and TMB | Colorimetry and FLI | Diagnosis | [ |
| ACP-Fe@DNCs | GPx and POD | GSH and H2O2 | Bioimaging | Diagnosis and therapy | [ |
| CC@PP | POD | H2O2 | FLI | Diagnosis and therapy | [ |
Table 1. MHNs for cancer diagnosis.
| Nanozyme | Activity | Substrate | Method | Application | Ref. |
|---|---|---|---|---|---|
| PW12@ZIF-67-Au | OXD | TMB | Colorimetry and electrochemistry | AFP detection | [ |
| i3k@Au/Cu | POD | TMB and H2O2 | Electrochemistry | CEA detection | [ |
| Cu2-xAgxS@liposome | POD | TMB and H2O2 | Colorimetry and fluorometry | CEA detection | [ |
| R-CQDs@Fe-NC | OXD | TMB | Colorimetry and fluorometry | PSA detection | [ |
| Mn3O4/Pd@Pt/HRP | HRP | H2O2 | Colorimetric immunoassay | HER2 detection | [ |
| AgNPs@GQDs-GOx | GOx and POD | Glucose | Bioimaging | Diagnosis and therapy | [ |
| Fe3O4@SiO2-APTES-NH2@Cyt-Cyt@FA | POD | H2O2 | Bioimaging and colorimetry | Diagnosis | [ |
| ZnMnFe2O4-PEG-FA | POD | H2O2 | PAI and MRI | Diagnosis and therapy | [ |
| Ang-IR780-MnO2-PLGA | GPx | GSH | PAI and FLI | Diagnosis and therapy | [ |
| IR808/DOX@Psome/MnO2 | POD | H2O2 | MRI and FLI | Diagnosis and therapy | [ |
| CPT/DM-FA | GPx and OXD | GSH and TMB | Colorimetry and FLI | Diagnosis | [ |
| ACP-Fe@DNCs | GPx and POD | GSH and H2O2 | Bioimaging | Diagnosis and therapy | [ |
| CC@PP | POD | H2O2 | FLI | Diagnosis and therapy | [ |
Fig. 2. Principle of Ni-MnFe-LDHs colorimetric detection for CA-125. In the absence of CA-125, Ni-MnFe-LDHs catalyze colorless TMB to oxidize into a blue product in the presence of hydrogen peroxide, the signal appears deep blue. When CA-125 is present in the sample, it is captured by aptamers on the Ni-MnFe-LDHs, resulting in a weakened blue signal. The higher the CA-125 concentration, the lighter the color. Reproduced with permission [99]. Copyright 2025, American Chemical Society.
Fig. 3. Application of M@GOx/Fe-HMON in the diagnosis and treatment of liver cancer. The superparamagnetism of M@GOx/Fe-HMON supports MRI-guided monitoring. M@GOx/Fe-HMON induces ferroptosis or disulfidation by responding to the TME. In glucose-rich areas, the GOx-POD cascade reaction is initiated to enhance ROS production and trigger ferroptosis; while in glucose-deficient areas, it induces nicotinamide adenine dinucleotide phosphate depletion and disulfide stress, ultimately leading to disulfide formation. Reproduced with permission [110]. Copyright 2025, Elsevier.
Fig. 4. Schematic illustration of GSH-responsive Z-M-LA@CM for cancer diagnosis and treatment. Z-M-LA@CM is activated by GSH, releasing the fluorescence of luminol gold nanoclusters quenched by MnO2, enabling cancer diagnosis. Subsequently, Mn2+ release is triggered, inducing a Fenton-like reaction and chemodynamic therapy (CDT). The CDT effect is further enhanced by NIR, facilitating combined CDT and PTT therapy. Reproduced with permission [121]. Copyright 2023, Elsevier.
Fig. 5. Muti-Pt/DMSN as a dual-mode platform for breast tumor detection by integrating POD colorimetric response and FLI. Multi-Pt/DMSN achieves selective targeting of the HER2 protein by integrating dual-fluorescent targeted ligands, including HER2 monoclonal antibodies and sk6Ea aptamers. The Multi-Pt/DMSN platform combines colorimetric sensing with FLI, enabling differentiation between HER2-positive cells and luminal A cell lines, triple-negative subtypes, and non-cancerous cells. Reproduced with permission [127]. Copyright 2025, Springer Nature.
| Nanozyme | Activity | Substrate | Application | References |
|---|---|---|---|---|
| PCN222-Mn@GOx/HA | GOx, POD and OXD | Glucose and H2O2 | CDT and PDT and immunotherapy | [ |
| CPL@G5-BS | SOD, POD and CAT | H2O2 | CDT and PTT | [ |
| Co/La-PB@MOF-199/GOx | GOx, POD, GPx and CAT | Glucose, GSH and H2O2 | CDT and PTT | [ |
| OFeCaSA-V@GA | POD and GPx | GSH and H2O2 | CDT and PDT | [ |
| MIrPHE | POD | H2O2 | CDT | [ |
| FessMOF/ActD-PEG | POD and GPx | GSH and H2O2 | CDT and immunotherapy | [ |
| FMMPG | POD | H2O2 | CDT and PDT | [ |
| PtPd@PMO@SNP@Au | GOx, POD, OXD and CAT | Glucose and H2O2 | CDT, PTT and GT | [ |
| DMSN@CoFe2O4/GOx-PCM | GOx, POD, GPx and CAT | Glucose, GSH and H2O2 | CDT and PTT | [ |
| Au2Pt@PMO@ICG Janus | POD and CAT | H2O2 | CDT, PDT and PTT | [ |
| PCN-224@Au@MnO2@HA | POD, GPx and CAT | GSH and H2O2 | CDT and PDT | [ |
| OPBP1-N-PCNS | POD | H2O2 | CDT and immunotherapy | [ |
| CeMn-V DAs/EGCG | POD | H2O2 | CDT and PTT | [ |
| Fe/Cu-MOF-199/GOx@PDA | POD, GPx and CAT | H2O2 and GSH | CDT and PTT | [ |
| Pd/Cu SAzyme@Dzy | POD and GPx | H2O2 and GSH | CDT and gene therapy | [ |
| DNFs@ZnMn | CAT | H2O2 | PDT and gene therapy | [ |
| MnO2@CeOx-GAMP | SOD, GPx and POD | H2O2 and GSH | CDT and gene therapy | [ |
Table 2. MHNs for cancer therapy.
| Nanozyme | Activity | Substrate | Application | References |
|---|---|---|---|---|
| PCN222-Mn@GOx/HA | GOx, POD and OXD | Glucose and H2O2 | CDT and PDT and immunotherapy | [ |
| CPL@G5-BS | SOD, POD and CAT | H2O2 | CDT and PTT | [ |
| Co/La-PB@MOF-199/GOx | GOx, POD, GPx and CAT | Glucose, GSH and H2O2 | CDT and PTT | [ |
| OFeCaSA-V@GA | POD and GPx | GSH and H2O2 | CDT and PDT | [ |
| MIrPHE | POD | H2O2 | CDT | [ |
| FessMOF/ActD-PEG | POD and GPx | GSH and H2O2 | CDT and immunotherapy | [ |
| FMMPG | POD | H2O2 | CDT and PDT | [ |
| PtPd@PMO@SNP@Au | GOx, POD, OXD and CAT | Glucose and H2O2 | CDT, PTT and GT | [ |
| DMSN@CoFe2O4/GOx-PCM | GOx, POD, GPx and CAT | Glucose, GSH and H2O2 | CDT and PTT | [ |
| Au2Pt@PMO@ICG Janus | POD and CAT | H2O2 | CDT, PDT and PTT | [ |
| PCN-224@Au@MnO2@HA | POD, GPx and CAT | GSH and H2O2 | CDT and PDT | [ |
| OPBP1-N-PCNS | POD | H2O2 | CDT and immunotherapy | [ |
| CeMn-V DAs/EGCG | POD | H2O2 | CDT and PTT | [ |
| Fe/Cu-MOF-199/GOx@PDA | POD, GPx and CAT | H2O2 and GSH | CDT and PTT | [ |
| Pd/Cu SAzyme@Dzy | POD and GPx | H2O2 and GSH | CDT and gene therapy | [ |
| DNFs@ZnMn | CAT | H2O2 | PDT and gene therapy | [ |
| MnO2@CeOx-GAMP | SOD, GPx and POD | H2O2 and GSH | CDT and gene therapy | [ |
Fig. 6. In vivo antitumor efficacy of the DCM. (a) Schematic depiction of the in vivo therapy. (b) Blood circulation curve of DCM nanozymes after intravenous injection. (c) Biodistribution of DCM nanozymes in major organs and tumors at different time points. (d) The tumor volume changes in the mice under different treatments. (e) Average weight and (f) photographs of tumors in different groups after the 14-day treatment period. (g) The body weight of mice in each group was assessed every 2 days. (h) Histological images of tumor slices stained with Hematoxylin-Eosin (HE) staining, and (i) Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) in different groups collected from tumor-bearing mice at day 14. Reproduced with permission [154]. Copyright 2025, Elsevier.
Fig. 7. The biodistribution and in vivo antitumor effect of ZFPG NPs in PC-3 tumor-bearing male Balb/c nude mice. (a) In vivo imaging of Cy5.5 labeled ZFPG NPs in PC-3-bearing mice with or without MF irradiation; (b) fluorescence intensity of the tumor sites after different treatments at various time points; (c) biodistribution of ZFP and ZFPG NPs with or without 24 h of magnetic field (MF) irradiation; (d) T2-weighted MRI of mice treated with Control, ZFP, ZFP + MF, ZFPG, and ZFPG + MF, as well as the gray values of tumor tissues after these treatments; (e) the treatment illustration of PC-3 tumor model and experimental design; (f) body weight curves of mice after different treatments; (g) relative tumor volume curves of mice after different treatments; (h) photograph of tumors after 14 days treatment in different groups; (i) representative digital images of HE, TUNEL, and Ki-67 staining of tumor tissues from different groups; and (j) histological changes of major organs after 14 days of treatments were evaluated by typical HE staining. Reproduced with permission [162]. Copyright 2025, Springer Nature.
Fig. 8. In vivo therapeutic efficacy evaluation of RNF@CM. (A) In vivo FLI of T24 tumor-bearing mice at different times after treatment. (B) FLI of the tumor tissues. (C) FLI of organs and tumors. (D) Representative images of tumors. (E) Tumor volumes of mice groups with intravenous injection of different nanocomposites every 2 days. (F) HE and TUNEL staining of the tumor tissues after various treatments. Reproduced with permission [172]. Copyright 2025, John Wiley and Sons.
Fig. 9. In vivo antitumor therapeutic effect of IrOx-P. (A) Schematic illustration of treatment and efficacy evaluation. (B) Mice body weight changes after different treatments. (C-E) Image and quantification of tumor growth after different treatments. (F) Representative immunofluorescent staining images for vascular endothelial growth factor (VEGF), CD31 and (H) vascular cell adhesion molecule 1 (VCAM-1) in tumor tissues after different treatments. Semi-quantitative analysis for expression levels of VEGF (G) and VCAM-1 (I). (J) Immunohistochemical staining of GPX4 and fluorescence staining of ROS after different treatments. Reproduced with permission [178]. Copyright 2025, Elsevier.
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