Issue

Vol. 18 (2026)

Confined Synthesis of Axial Chlorine Coordinated Single-Atom Nanozyme Within Liposomes for Sensitive Immunoassay

https://doi.org/10.1007/s40820-026-02136-5
Chenchen Chu
Materials Artificial Intelligence Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People’s Republic of China
Mingyang Jiang
Materials Artificial Intelligence Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People’s Republic of China
Yubei Zhang
Materials Artificial Intelligence Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People’s Republic of China
Kun Feng
Nanjing University, 210023 Nanjing, People’s Republic of China
Chaolei Hua
Materials Artificial Intelligence Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People’s Republic of China
Lie Wu
State Key Laboratory of Advanced Refractories, Wuhan University of Science and Technology, 430081 Wuhan, People’s Republic of China
Yijie Chen
Materials Artificial Intelligence Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People’s Republic of China
Ling Ji
Department of Laboratory Medicine, Peking University Shenzhen Hospital, 518055 Shenzhen, People’s Republic of China
Xitong Gao
Research Center for Cloud Computing, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 518055 Shenzhen, People’s Republic of China
Xue‑Feng Yu
Materials Artificial Intelligence Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People’s Republic of China
Shengyong Geng
Materials Artificial Intelligence Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People’s Republic of China
Wenhua Zhou
Materials Artificial Intelligence Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People’s Republic of China

Corresponding Author: Wenhua Zhou

wh.zhou@siat.ac.cn

Nano-Micro Letters, Vol. 18 (2026), Article Number: 293

Abstract

Single-atom nanozymes (SANs) are considered as the most promising candidates for signal amplification in biosensing applications. However, maintaining the integrity of active sites during functionalization while preserving catalytic performance in biological environments remains a critical challenge. Here, we present a low-temperature-photochemical synthesis strategy for constructing platinum single-atoms within liposomes (PtSANs@Lipo), achieving atomic-level regulation of SANs active sites through axial chlorine (Cl) coordination engineering. The PtN3Cl2 coordination structure, validated by synchrotron X-ray absorption spectroscopy, induces optimal d-band center modulation giving a remarkably low determining step energy barrier compared to conventional PtN3 configurations. This architecture further enables non-contact functionalization via liposomal encapsulation, fully preserving catalytic activity while preventing catalytic sites occupation by antibody, thereby reducing the Michaelis constant (Km) value by 50-fold compared to direct modification onto Pt single-atoms. The constructed immunosensor based on PtSANs@Lipo demonstrates highly sensitive detection of viral pathogens, including influenza A virus H1N1, SARS-CoV-2, and influenza B virus antigens with limits of detection as low as 0.42, 2.23, and 0.36 fg mL−1, respectively. This work establishes a paradigm for bio-adaptive nanozyme design through synergistic coordination engineering and liposomal functionalization architectures, and may thus provide a universal approach for signal amplification in point-of-care diagnostics.


Highlights:
1 Axial chlorine coordination engineering constructs PtN3Cl2 single-atom nanozymes inside liposomes via a low-temperature photochemical method.
2 The unique structure lowers the reaction energy barrier and enables antibody conjugation without blocking active sites, reducing Km by 50-fold.
3 The resulting immunosensor achieves ultra-sensitive detection of viral antigens with detection limits as low as 0.36 fg mL-1.

Keywords

Single-atom nanozyme Axial chlorine coordination Liposomes Photochemical reduction Immunoassay
Chu, Chenchen, Mingyang Jiang, Yubei Zhang, Kun Feng, Chaolei Hua, Lie Wu, Yijie Chen, Ling Ji, Xitong Gao, Xue‑Feng Yu, Shengyong Geng, and Wenhua Zhou. 2026. “Confined Synthesis of Axial Chlorine Coordinated Single-Atom Nanozyme Within Liposomes for Sensitive Immunoassay”. Nano-Micro Letters 18 (March):293. https://doi.org/10.1007/s40820-026-02136-5.
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References
  1. S. Ding, J.A. Barr, Z. Lyu, F. Zhang, M. Wang et al., Effect of phosphorus modulation in iron single-atom catalysts for peroxidase mimicking. Adv. Mater. 36(10), e2209633 (2024). https://doi.org/10.1002/adma.202209633
  2. E.M. Hamed, L. He, V. Rai, S. Hu, S.F.Y. Li, Copper single-atom nanozyme mimicking galactose oxidase with superior catalytic activity and selectivity. Small 20(49), e2405986 (2024). https://doi.org/10.1002/smll.202405986
  3. E.M. Hamed, F.M. Fung, S.F.Y. Li, Zinc single-atom nanozyme as carbonic anhydrase mimic for CO2 capture and conversion. ACS Mater. Au 5(2), 377–384 (2025). https://doi.org/10.1021/acsmaterialsau.4c00156
  4. T. Chen, H. Guo, X. Wen, J. Yu, H. Shi et al., Phosphatase-like nanozymes with tailed selectivity and enhanced activity for endotoxin sensing. Talanta 298, 128860 (2026). https://doi.org/10.1016/j.talanta.2025.128860
  5. B. Xu, Y. Cui, W. Wang, S. Li, C. Lyu et al., Immunomodulation-enhanced nanozyme-based tumor catalytic therapy. Adv. Mater. 32(33), e2003563 (2020). https://doi.org/10.1002/adma.202003563
  6. R. Wang, X. Ma, E.M. Hamed, B. Cao, L. Wang et al., Deciphering of laccase-like activity ruthenium single-atom nanozyme for identification/quantification and remediation of phenolic pollutants. Sens. Actuators B Chem. 426, 137112 (2025). https://doi.org/10.1016/j.snb.2024.137112
  7. E.M. Hamed, F.M. Fung, S.F.Y. Li, Bimetallic Cu/Zn single-atom nanozyme with superoxide dismutase-like activity. Small 21(36), e03879 (2025). https://doi.org/10.1002/smll.202503879
  8. Y. Ai, Z.-N. Hu, X. Liang, H.-B. Sun, H. Xin et al., Recent advances in nanozymes: from matters to bioapplications. Adv. Funct. Mater. 32(14), 2110432 (2022). https://doi.org/10.1002/adfm.202110432
  9. Z. Yu, Z. Xu, R. Zeng, M. Xu, H. Zheng et al., D-band-center-engineered platinum-based nanozyme for personalized pharmacovigilance. Angew. Chem. 137(2), e202414625 (2025). https://doi.org/10.1002/ange.202414625
  10. Z. Yu, Z. Xu, R. Zeng, M. Xu, H. Zheng et al., D-band-center-engineered platinum-based nanozyme for personalized pharmacovigilance. Angew. Chem. Int. Ed. Engl. 137(2), e202414625 (2025). https://doi.org/10.1002/ange.202414625
  11. R. Zeng, Q. Gao, L. Xiao, W. Wang, Y. Gu et al., Precise tuning of the D-band center of dual-atomic enzymes for catalytic therapy. J. Am. Chem. Soc. 146(14), 10023–10031 (2024). https://doi.org/10.1021/jacs.4c00791
  12. H. Gu, J. Li, P. Dai, T. Sun, C. Chen et al., Polyphenol oxidase-like nanozymes. Adv. Mater. 37(43), e09346 (2025). https://doi.org/10.1002/adma.202509346
  13. J. Li, X. Cai, P. Jiang, H. Wang, S. Zhang et al., Co-based nanozymatic profiling: advances spanning chemistry, biomedical, and environmental sciences. Adv. Mater. 36(8), e2307337 (2024). https://doi.org/10.1002/adma.202307337
  14. M. Tang, J. Ni, Z. Yue, T. Sun, C. Chen et al., Polyoxometalate-nanozyme-integrated nanomotors (POMotors) for self-propulsion-promoted synergistic photothermal-catalytic tumor therapy. Angew. Chem. Int. Ed. 63(6), e202315031 (2024). https://doi.org/10.1002/anie.202315031
  15. Z. Fu, K. Fan, X. He, Q. Wang, J. Yuan et al., Single-atom-based nanoenzyme in tissue repair. ACS Nano 18(20), 12639–12671 (2024). https://doi.org/10.1021/acsnano.4c00308
  16. S. Zhang, Y. Li, S. Sun, L. Liu, X. Mu et al., Single-atom nanozymes catalytically surpassing naturally occurring enzymes as sustained stitching for brain trauma. Nat. Commun. 13(1), 4744 (2022). https://doi.org/10.1038/s41467-022-32411-z
  17. Z. Guo, J. Hong, N. Song, M. Liang, Single-atom nanozymes: from precisely engineering to extensive applications. Acc. Mater. Res. 5(3), 347–357 (2024). https://doi.org/10.1021/accountsmr.3c00250
  18. C. Peng, R. Pang, J. Li, E. Wang, Current advances on the single-atom nanozyme and its bioapplications. Adv. Mater. 36(10), e2211724 (2024). https://doi.org/10.1002/adma.202211724
  19. E.M. Hamed, F.M. Fung, S.F.Y. Li, Unleashing the potential of single-atom nanozymes: catalysts for the future. ACS Sens. 9(8), 3840–3847 (2024). https://doi.org/10.1021/acssensors.4c00630
  20. E.M. Hamed, V. Rai, S.F.Y. Li, Single-atom nanozymes with peroxidase-like activity: a review. Chemosphere 346, 140557 (2024). https://doi.org/10.1016/j.chemosphere.2023.140557
  21. E.M. Hamed, M.M. Elsaady, S.F.Y. Li, Single-atom nanozymes in analytical chemistry: opportunities and challenges. Anal. Chem. 97(48), 26313–26325 (2025). https://doi.org/10.1021/acs.analchem.5c05006
  22. P. Muhammad, A. Zada, J. Rashid, S. Hanif, Y. Gao et al., Defect engineering in nanocatalysts: from design and synthesis to applications. Adv. Funct. Mater. 34(29), 2314686 (2024). https://doi.org/10.1002/adfm.202314686
  23. J. Shen, J. Chen, Y. Qian, X. Wang, D. Wang et al., Atomic engineering of single-atom nanozymes for biomedical applications. Adv. Mater. 36(21), e2313406 (2024). https://doi.org/10.1002/adma.202313406
  24. X. Zhang, G. Li, G. Chen, D. Wu, X. Zhou et al., Single-atom nanozymes: a rising star for biosensing and biomedicine. Coord. Chem. Rev. 418, 213376 (2020). https://doi.org/10.1016/j.ccr.2020.213376
  25. L. Jiao, W. Xu, Y. Wu, H. Yan, W. Gu et al., Single-atom catalysts boost signal amplification for biosensing. Chem. Soc. Rev. 50(2), 750–765 (2021). https://doi.org/10.1039/d0cs00367k
  26. S. Wei, M. Sun, J. Huang, Z. Chen, X. Wang et al., Axial chlorination engineering of single-atom nanozyme: Fe–N4Cl catalytic sites for efficient peroxidase-mimicking. J. Am. Chem. Soc. 146(48), 33239–33248 (2024). https://doi.org/10.1021/jacs.4c13335
  27. H.-Y. Lee, S.H.R. Shin, L.L. Abezgauz, S.A. Lewis, A.M. Chirsan et al., Integration of gold nanops into bilayer structures via adaptive surface chemistry. J. Am. Chem. Soc. 135(16), 5950–5953 (2013). https://doi.org/10.1021/ja400225n
  28. Y. Yu, Z. Zhu, H. Huang, Surface engineered single-atom systems for energy conversion. Adv. Mater. 36(16), e2311148 (2024). https://doi.org/10.1002/adma.202311148
  29. L. Zhang, M. Zhou, A. Wang, T. Zhang, Selective hydrogenation over supported metal catalysts: from nanops to single atoms. Chem. Rev. 120(2), 683–733 (2020). https://doi.org/10.1021/acs.chemrev.9b00230
  30. X.-F. Yang, A. Wang, B. Qiao, J. Li, J. Liu et al., Single-atom catalysts: a new frontier in heterogeneous catalysis. Acc. Chem. Res. 46(8), 1740–1748 (2013). https://doi.org/10.1021/ar300361m
  31. N. Kang, L. Liao, X. Zhang, Z. He, B. Yu et al., Engineering the axial coordination of cobalt single atom catalysts for efficient photocatalytic hydrogen evolution. Nano Res. 17(6), 5114–5121 (2024). https://doi.org/10.1007/s12274-024-6411-1
  32. J.-B. Pan, B.-H. Wang, S. Shen, L. Chen, S.-F. Yin, Introducing bidirectional axial coordination into BiVO4 @metal phthalocyanine core-shell photoanodes for efficient water oxidation. Angew. Chem. Int. Ed. Engl. 62(38), e202307246 (2023). https://doi.org/10.1002/anie.202307246
  33. D. Liu, X. Wan, J. Shui, Tailoring oxygen reduction reaction on M-N-C catalysts via axial coordination engineering. Small 20(50), e2406078 (2024). https://doi.org/10.1002/smll.202406078
  34. W. Song, C. Xiao, J. Ding, Z. Huang, X. Yang et al., Review of carbon support coordination environments for single metal atom electrocatalysts (SACS). Adv. Mater. 36(1), e2301477 (2024). https://doi.org/10.1002/adma.202301477
  35. L. Yin, M. Sun, S. Zhang, Y. Huang, B. Huang et al., Chlorine axial coordination activated lanthanum single atoms for efficient oxygen electroreduction with maximum utilization. Adv. Mater. 37(7), e2416387 (2025). https://doi.org/10.1002/adma.202416387
  36. S. Ren, Y. Wang, L. Shi, X. Xu, S. Zhong et al., Transforming plastics to single atom catalysts for peroxymonosulfate activation: axial chloride coordination intensified electron transfer pathway. Adv. Mater. 37(8), e2415339 (2025). https://doi.org/10.1002/adma.202415339
  37. Z. Zhang, Z. Feng, X. Zhao, D. Jean, Z. Yu et al., Functionalization and higher-order organization of liposomes with DNA nanostructures. Nat. Commun. 14(1), 5256 (2023). https://doi.org/10.1038/s41467-023-41013-2
  38. C. Wang, X. Lan, L. Zhu, Y. Wang, X. Gao et al., Construction strategy of functionalized liposomes and multidimensional application. Small 20(25), e2309031 (2024). https://doi.org/10.1002/smll.202309031
  39. V.P. Torchilin, Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov. 4(2), 145–160 (2005). https://doi.org/10.1038/nrd1632
  40. N. Filipczak, J. Pan, S.S.K. Yalamarty, V.P. Torchilin, Recent advancements in liposome technology. Adv. Drug Deliv. Rev. 156, 4–22 (2020). https://doi.org/10.1016/j.addr.2020.06.022
  41. M. Lyu, M. Luo, J. Li, O.U. Akakuru, X. Fan et al., Personalized carbon monoxide-loaded biomimetic single-atom nanozyme for ferroptosis-enhanced FLASH radioimmunotherapy. Adv. Funct. Mater. 33(51), 2306930 (2023). https://doi.org/10.1002/adfm.202306930
  42. X.T. Le, N.T. Nguyen, W.T. Lee, Y. Yang, H.-G. Choi et al., Peroxidase-mimicking iron-based single-atom upconversion photocatalyst for enhancing chemodynamic therapy. Adv. Funct. Mater. 34(34), 2401893 (2024). https://doi.org/10.1002/adfm.202401893
  43. J.-H. Lee, Y. Shin, W. Lee, K. Whang, D. Kim et al., General and programmable synthesis of hybrid liposome/metal nanops. Sci. Adv. 2(12), e1601838 (2016). https://doi.org/10.1126/sciadv.1601838
  44. H. Zhang, G. Liu, L. Shi, J. Ye, Single-atom catalysts: emerging multifunctional materials in heterogeneous catalysis. Adv. Energy Mater. 8, 1701343 (2018). https://doi.org/10.1002/aenm.201701343
  45. Y. Zhang, J. Yang, R. Ge, J. Zhang, J.M. Cairney et al., The effect of coordination environment on the activity and selectivity of single-atom catalysts. Coord. Chem. Rev. 461, 214493 (2022). https://doi.org/10.1016/j.ccr.2022.214493
  46. J. Chang, W. Jing, X. Yong, A. Cao, J. Yu et al., Synthesis of ultrahigh-metal-density single-atom catalysts via metal sulfide-mediated atomic trapping. Nat. Synth 3(11), 1427–1438 (2024). https://doi.org/10.1038/s44160-024-00607-4
  47. D. Huang, L. Yin, X. Lu, S. Lin, Z. Niu et al., Directional electron transfer mechanisms with graphene quantum dots as the electron donor for photodecomposition of perfluorooctane sulfonate. Chem. Eng. J. 323, 406–414 (2017). https://doi.org/10.1016/j.cej.2017.04.124
  48. H. Wei, K. Huang, D. Wang, R. Zhang, B. Ge et al., Iced photochemical reduction to synthesize atomically dispersed metals by suppressing nanocrystal growth. Nat. Commun. 8(1), 1490 (2017). https://doi.org/10.1038/s41467-017-01521-4
  49. F. Maurer, J. Jelic, J. Wang, A. Gänzler, P. Dolcet et al., Tracking the formation, fate and consequence for catalytic activity of Pt single sites on CeO2. Nat. Catal. 3(10), 824–833 (2020). https://doi.org/10.1038/s41929-020-00508-7
  50. X. Liu, X. Song, G. Jiang, L. Tao, Z. Jin et al., Pt single-atom collaborate with Pt atom-clusters by an in-situ confined strategy for accelerating electrocatalytic hydrogen evolution. Chem. Eng. J. 481, 148430 (2024). https://doi.org/10.1016/j.cej.2023.148430
  51. Z. Xu, J. Jiang, Y. Li, T. Hu, J. Gu et al., Shape-regulated photothermal-catalytic tumor therapy using Polydopamine@Pt nanozymes with the elicitation of an immune response. Small 20(20), e2309096 (2024). https://doi.org/10.1002/smll.202309096
  52. K. Deng, H. Hu, Y. Li, X. Li, H. Deng et al., Mechanistic investigation and dual-mode colorimetric-chemiluminescent detection of glyphosate based on the specific inhibition of Fe3O4@Cu nanozyme peroxidase-like activity. Food Chem. 443, 138501 (2024). https://doi.org/10.1016/j.foodchem.2024.138501
  53. B.H.J. Hofstee, On the evaluation of the constants Vm and KM in enzyme reactions. Science 116(3013), 329–331 (1952). https://doi.org/10.1126/science.116.3013.329
  54. M. Sela, M. Poley, P. Mora-Raimundo, S. Kagan, A. Avital et al., Brain-targeted liposomes loaded with monoclonal antibodies reduce alpha-synuclein aggregation and improve behavioral symptoms in Parkinson’s disease. Adv. Mater. 35(51), e2304654 (2023). https://doi.org/10.1002/adma.202304654
  55. A.B. Ganganboina, A.D. Chowdhury, I.M. Khoris, F. Nasrin, K. Takemura et al., Dual modality sensor using liposome-based signal amplification technique for ultrasensitive norovirus detection. Biosens. Bioelectron. 157, 112169 (2020). https://doi.org/10.1016/j.bios.2020.112169
  56. G. Seo, G. Lee, M.J. Kim, S.-H. Baek, M. Choi et al., Rapid detection of COVID-19 causative virus (SARS-CoV-2) in human nasopharyngeal swab specimens using field-effect transistor-based biosensor. ACS Nano 14(4), 5135–5142 (2020). https://doi.org/10.1021/acsnano.0c02823
  57. J. Shang, Y. Wang, Y. Pang, M. Yu, Y. Wang et al., Point-of-care diagnosis of respiratory viruses at single-nucleotide resolution with an autocatalytic rolling circle amplification system. Angew. Chem. Int. Ed. 64(52), e18925 (2025). https://doi.org/10.1002/anie.202518925
  58. A. Piriya V S, P. Joseph, K. Daniel S C G, S. Lakshmanan, T. Kinoshita et al., Colorimetric sensors for rapid detection of various analytes. Mater. Sci. Eng. C Mater. Biol. Appl. 78, 1231–1245 (2017). https://doi.org/10.1016/j.msec.2017.05.018
  59. R. Cui, H. Tang, Q. Huang, T. Ye, J. Chen et al., AI-assisted smartphone-based colorimetric biosensor for visualized, rapid and sensitive detection of pathogenic bacteria. Biosens. Bioelectron. 259, 116369 (2024). https://doi.org/10.1016/j.bios.2024.116369
  60. S. Wang, Y. Zhu, Z. Zhou, Y. Luo, Y. Huang et al., Integrated ultrasound-enrichment and machine learning in colorimetric lateral flow assay for accurate and sensitive clinical Alzheimer’s biomarker diagnosis. Adv. Sci. 11(42), 2406196 (2024). https://doi.org/10.1002/advs.202406196
  61. T. He, Z. Zhang, H. Zhang, Z. Zhang, J. Xie et al., Bag of tricks for image classification with convolutional neural networks. 2019 IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR)., 558–567. IEEE (2020). https://doi.org/10.1109/CVPR.2019.00065
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