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Iron–silver-modified quantum dots act as efficient catalysts in anti-cancer multitherapy through controlled, ultrasound-induced oxidation

Nature Nanotechnology volume 20, pages 1098–1107 (2025)Cite this article

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Abstract

Chemodynamic therapy and sonodynamic therapy are two promising tumour therapeutic strategies. However, lack of highly effective sonosensitizers and control over chemodynamic therapy limit their application. Here we synthesize silver-doped zinc selenide quantum dots with atomically dispersed superficial Fe and show that they act as efficient sonosensitizers, catalysers and immunoreagents. Surface modification with an in situ self-assembly peptide drives accumulation in tumours. Superficial FeIII remains stable and converts to FeII only under ultrasonic processing, reverting to FeIII upon ultrasound cessation. Under ultrasound stimulation, superficial Fe undergoes valence change with concomitant amelioration of the hypoxic tumour microenvironment and production of sonodynamic therapy-beneficial hydroxyl radicals. Furthermore, silver doping suppressed nonradiative recombination of excitons, leading to improved production of singlet oxygen. Meanwhile, selenium promotes robust systemic immune responses for the inhibition of tumour metastases. This nano-platform allows control of valence switching of atomically dispersed catalysts, representing an effective tool for chemodynamic/sonodynamic/immunotherapy.

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Fig. 1: Characterization of FAQD.
Fig. 2: 1O2 detection and mechanism exploration.
Fig. 3: Characterization of atomically dispersed Fe with controllable variable valence and ROS detection.
Fig. 4: Characterization of FAQD-1 transformation.
Fig. 5: Tumour retention of FAQD-1 and the treatment for tumours under US.
Fig. 6: The multi-enhanced chemodynamic/sonodynamic/immunotherapy.

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Data availability

All relevant data during the study are available from the corresponding authors upon request. Source data are provided with this paper.

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Acknowledgements

This research was supported by the National Natural Science Foundation of China (52272186, 51631001, 51902023, 51702016, 21674027, 21704020, 31870998, 51573032 and 22305139), the National Science Fund for Distinguished Young Scholars (51725302) and the Science Fund for Creative Research Groups of the National Natural Science Foundation of China (11621505).

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Authors and Affiliations

  1. Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Institute of Medical-Industrial Integration, Beijing Key Laboratory of Structurally Controllable Advanced Functional Materials and Green Applications, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, China

    Dong Wang, Lei Ji, You Li, Meng Xu & Jiatao Zhang

  2. CAS Center for Excellence in Nanoscience, Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing, China

    Hao Wang & Zeng-Ying Qiao

  3. Dipartimento di Scienza dei Materiali, Universitàdegli Studi di Milano Bicocca, Milano, Italy

    Sergio Brovelli

  4. Department of Chemistry, Tsinghua University, Beijing, China

    Yadong Li

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Contributions

D.W., S.B., Z.-Y.Q. and J.Z. conceived and designed the experiments. D.W., L.J., You Li and Z.-Y.Q. performed the experiments. D.W., M.X., H.W., S.B., Z.-Y.Q., J.Z. and Yadong Li analysed the results and discussed the paper. D.W., S.B., Z.-Y.Q. and J.Z. wrote the paper. Z.-Y.Q. and J.Z. supervised the entire project.

Corresponding authors

Correspondence to Sergio Brovelli, Zeng-Ying Qiao or Jiatao Zhang.

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The authors declare no competing interests.

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Nature Nanotechnology thanks Kelong Ai, Peng Hou and Huixiong Xu for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 Design of the FAQD-1 and the schematic illustration of therapy.

(a) Schematic process of controllable synthesis of FAQD-1. (b) Schematic illustration of multi-enhanced chemodynamic/sonodynamic/immuno therapy of FAQD-1 under US.

Extended Data Fig. 2 ROS detection, cytotoxicity test and retention study in vitro.

(a) Confocal Laser Scanning Microscope images (scale bar = 50 μm) and (b) flow cytometric quantification of Hela cells stained with DCFH-DA after treated by different nanomaterials with 25 μg/mL (n = 3 experimental repeats, mean ± SD, two-way ANOVA; the P value is noted). (c) JC-1 staining (scale bar = 100 μm) and (d) Annexin V-FITC and PI staining (scale bar = 20 μm) of HeLa cells with different treatments (the concentration of the nanomaterials is 25 μg/mL). (e) Cytotoxicity test of Hela cells from under US (1 W/cm2) for 3 min with different formulations (n = 5 experimental repeats, mean ± SD). (f) TEM of MCS treated with FAQD-1 in the presence of MMP, Red arrows indicate the nanoaggregates (scale bar = 500 nm). (g) The retention of Zn element in MCS after co-incubation with FAQD-1 or FAQD-2 in the presence of MMP.

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Supplementary Figs. 1–89 and Tables 1–5.

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Source data for Supplementary Figs. 3–9, 11–28, 31, 33, 37–41, 44–48, 50, 51, 53, 54, 57–65, 67, 69–74, 77, 79, 81, 83 and 85–89.

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Wang, D., Ji, L., Li, Y. et al. Iron–silver-modified quantum dots act as efficient catalysts in anti-cancer multitherapy through controlled, ultrasound-induced oxidation. Nat. Nanotechnol. 20, 1098–1107 (2025). https://doi.org/10.1038/s41565-025-01943-y

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