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Valence-tailored copper-based nanoparticles for enhanced chemodynamic therapy through prolonged ROS generation and potentiated GSH depletion

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Abstract

Chemodynamic therapy (CDT), an inventive approach to cancer treatment, exploits innate chemical processes to trigger cell death through the generation of reactive oxygen species (ROS). While offering advantages over conventional treatments, the optimization of CDT efficacy presents challenges stemming from suboptimal catalytic efficiency and the counteractive ROS scavenging effect of intracellular glutathione (GSH). In this study, we aim to address this dual challenge by delving into the role of copper valence states in CDT. Leveraging the unique attributes of copper-based nanoparticles, especially zero-valent copper nanoparticles (CuPd NPs), we aim to enhance the therapeutic potential of CDT. Our experiments reveal that zero-valent CuPd NPs outperform divalent copper nanoparticles (Ox-CuPd NPs) by displaying superior catalytic performance and sustaining ROS generation through a dual approach integrating peroxidase-like (POD-like) activity and Cu+ release. Notably, zero-valent NPs exhibit enhanced GSH depletion compared to their divalent counterparts, thereby intensifying CDT and inducing ferroptosis, ultimately resulting in high-efficiency tumor growth inhibition. These findings reveal the impact of valences on CDT, providing novel insights for the optimization and design of CDT agents.

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References

  1. Tang, Z. M.; Liu, Y. Y.; He, M. Y.; Bu, W. B. Chemodynamic therapy: Tumour microenvironment-mediated fenton and fenton-like reactions. Angew. Chem., Int. Ed. 2019, 58, 946–956.

    Article  CAS  Google Scholar 

  2. Fang, H. Y.; Wang, X. Y.; Lan, X. L.; Jiang, D. W. Positron emission tomography imaging sheds new light on hypoxia and antitumor therapies. Interdiscip. Med. 2023, 1, e20230002.

    Article  Google Scholar 

  3. Chang, M. Y.; Wang, M.; Wang, M. F.; Shu, M. M.; Ding, B. B.; Li, C. X.; Pang, M. L.; Cui, S. Z.; Hou, Z. Y.; Lin, J. A multifunctional cascade bioreactor based on hollow-structured Cu2MoS4 for synergetic cancer chemo-dynamic therapy/starvation therapy/phototherapy/immunotherapy with remarkably enhanced efficacy. Adv. Mater. 2019, 31, 1905271.

    Article  CAS  Google Scholar 

  4. Ma, B. J.; Wang, S.; Liu, F.; Zhang, S.; Duan, J. Z.; Li, Z.; Kong, Y.; Sang, Y. H.; Liu, H.; Bu, W. B. et al. Self-assembled copper-amino acid nanoparticles for in situ glutathione “AND” H2O2 sequentially triggered chemodynamic therapy. J. Am. Chem. Soc. 2019, 141, 849–857.

    Article  CAS  PubMed  Google Scholar 

  5. Lin, L. S.; Huang, T.; Song, J. B.; Ou, X. Y.; Wang, Z. T.; Deng, H. Z.; Tian, R.; Liu, Y. J.; Wang, J. F.; Liu, Y. et al. Synthesis of copper peroxide nanodots for H2O2 self-supplying chemodynamic therapy. J. Am. Chem. Soc. 2019, 141, 9937–9945.

    Article  CAS  PubMed  Google Scholar 

  6. Zhang, H. L.; Li, J. J.; Chen, Y.; Wu, J. Y.; Wang, K.; Chen, L. J.; Wang, Y.; Jiang, X. W.; Liu, Y. Y.; Wu, Y. L. et al. Magnetoelectrically enhanced intracellular catalysis of FePt-FeC heterostructures for chemodynamic therapy. Adv. Mater. 2021, 33, 2100472.

    Article  CAS  Google Scholar 

  7. Ou, J. F.; Tian, H.; Wu, J. Y.; Gao, J. B.; Jiang, J. M.; Liu, K.; Wang, S. H.; Wang, F.; Tong, F.; Ye, Y. C. et al. MnO2-based nanomotors with active Fenton-like Mn2+ delivery for enhanced chemodynamic therapy. ACS Appl. Mater. Interfaces 2021, 13, 38050–38060.

    Article  CAS  PubMed  Google Scholar 

  8. Xiao, T. T.; He, M. J.; Xu, F.; Fan, Y.; Jia, B. Y.; Shen, M. W.; Wang, H.; Shi, X. Y. Macrophage membrane-camouflaged responsive polymer nanogels enable magnetic resonance imaging-guided chemotherapy/chemodynamic therapy of orthotopic glioma. ACS Nano 2021, 15, 20377–20390.

    Article  CAS  PubMed  Google Scholar 

  9. Ding, B. B.; Zheng, P.; Jiang, F.; Zhao, Y. J.; Wang, M. F.; Chang, M. Y.; Ma, P.; Lin, J. MnOx nanospikes as nanoadjuvants and immunogenic cell death drugs with enhanced antitumor immunity and antimetastatic effect. Angew. Chem., Int. Ed. 2020, 59, 16381–16384.

    Article  CAS  Google Scholar 

  10. Ding, B. B.; Zheng, P.; Ma, P.; Lin, J. Manganese oxide nanomaterials: Synthesis, properties, and theranostic applications. Adv. Mater. 2020, 32, 1905823.

    Article  CAS  Google Scholar 

  11. Han, D.; Ding, B. B.; Zheng, P.; Yuan, M.; Bian, Y. L.; Chen, H.; Wang, M. F.; Chang, M. Y.; Kheraif, A. A. A.; Ma, P. et al. NADPH oxidase-like nanozyme for high-efficiency tumor therapy through increasing glutathione consumption and blocking glutathione regeneration. Adv. Healthc. Mater., in press, DOI: https://doi.org/10.1002/adhm.202303309.

  12. Liang, S.; Xiao, X.; Bai, L. X.; Liu, B.; Yuan, M.; Ma, P.; Pang, M. L.; Cheng, Z. Y.; Lin, J. Conferring Ti-based MOFs with defects for enhanced sonodynamic cancer therapy. Adv. Mater. 2021, 33, 2100333.

    Article  CAS  Google Scholar 

  13. Liu, G. Y.; Zhu, J. W.; Guo, H.; Sun, A. H.; Chen, P.; Xi, L.; Huang, W.; Song, X. J.; Dong, X. C. Mo2C-derived polyoxometalate for NIR-II photoacoustic imaging-guided chemodynamic/photothermal synergistic therapy. Angew. Chem., Int. Ed. 2019, 58, 18641–18646.

    Article  CAS  Google Scholar 

  14. Wu, Q.; He, Z. G.; Wang, X.; Zhang, Q.; Wei, Q. C.; Ma, S. Q.; Ma, C.; Li, J. Y.; Wang, Q. G. Cascade enzymes within self-assembled hybrid nanogel mimicked neutrophil lysosomes for singlet oxygen elevated cancer therapy. Nat. Commun. 2019, 10, 240.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Tang, Z. M.; Zhao, P. R.; Wang, H.; Liu, Y. Y.; Bu, W. B. Biomedicine meets fenton chemistry. Chem. Rev. 2021, 121, 1981–2019.

    Article  CAS  PubMed  Google Scholar 

  16. Wang, Y. H.; Zhan, J.; Huang, J. Y.; Wang, X.; Chen, Z. H.; Yang, Z. M.; Li, J. Dynamic responsiveness of self - assembling peptide-based nano - drug systems. Interdiscip. Med. 2023, 1, e20220005.

    Article  Google Scholar 

  17. Wang, M.; Yang, C. Z.; Chang, M. Y.; Xie, Y. L.; Zhu, G. Q.; Qian, Y. R.; Zheng, P.; Sun, Q. Q.; Lin, J.; Li, C. X. Single-atom nanozymes based nanobee vehicle for autophagy inhibition-enhanced synergistic cancer therapy. Nano Today 2023, 52, 101981.

    Article  CAS  Google Scholar 

  18. Ren, X. Y.; Chen, D. X.; Wang, Y.; Li, H. F.; Zhang, Y. B.; Chen, H. Y.; Li, X.; Huo, M. F. Nanozymes-recent development and biomedical applications. J. Nanobiotechnology 2022, 20, 92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dong, H. J.; Du, W.; Dong, J.; Che, R. R.; Kong, F.; Cheng, W. L.; Ma, M.; Gu, N.; Zhang, Y. Depletable peroxidase-like activity of Fe3O4 nanozymes accompanied with separate migration of electrons and iron ions. Nat. Commun. 2022, 13, 5365.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wu, F.; Du, Y. Q.; Yang, J. N.; Shao, B. Y.; Mi, Z. S.; Yao, Y. F.; Cui, Y.; He, F.; Zhang, Y. Q.; Yang, P. Peroxidase-like active nanomedicine with dual glutathione depletion property to restore oxaliplatin chemosensitivity and promote programmed cell death. ACS Nano 2022, 16, 3647–3663.

    Article  CAS  PubMed  Google Scholar 

  21. Lu, J.; Jiang, Z. Y.; Ren, J.; Zhang, W.; Li, P.; Chen, Z. Z.; Zhang, W.; Wang, H.; Tang, B. One-pot synthesis of multifunctional carbon-based nanoparticle-supported dispersed Cu2+ disrupts redox homeostasis to enhance CDT. Angew. Chem., Int. Ed. 2022, 61, e202114373.

    Article  CAS  Google Scholar 

  22. Li, L.; Yang, Z.; Fan, W. P.; He, L. C.; Cui, C.; Zou, J. H.; Tang, W.; Jacobson, O.; Wang, Z. T.; Niu, G. et al. In situ polymerized hollow mesoporous organosilica biocatalysis nanoreactor for enhancing ROS-mediated anticancer therapy. Adv. Funct. Mater. 2020, 30, 1907716.

    Article  CAS  PubMed  Google Scholar 

  23. Brillas, E.; Baños, M. A.; Camps, S.; Arias, C.; Cabot, P. L.; Garrido, J. A.; Rodríguez, R. M. Catalytic effect of Fe2+, Cu2+ and UVA light on the electrochemical degradation of nitrobenzene using an oxygen-diffusion cathode. New J. Chem. 2004, 28, 314–322.

    Article  CAS  Google Scholar 

  24. Zhao, F.; Yu, H. Y.; Liang, L. Y.; Wang, C.; Shi, D. E.; Zhang, X. Y.; Ying, Y.; Cai, W.; Li, W. C.; Li, J. et al. Redox homeostasis disruptors based on metal-phenolic network nanoparticles for chemo/chemodynamic synergistic tumor therapy through activating apoptosis and cuproptosis. Adv. Healthc. Mater. 2023, 12, 2301346.

    Article  CAS  Google Scholar 

  25. Lin, L. S.; Song, J. B.; Song, L.; Ke, K. M.; Liu, Y. J.; Zhou, Z. J.; Shen, Z. Y.; Li, J.; Yang, Z.; Tang, W. et al. Simultaneous fenton-like ion delivery and glutathione depletion by MnO2-based nanoagent to enhance chemodynamic therapy. Angew. Chem., Int. Ed. 2018, 57, 4902–4906.

    Article  CAS  Google Scholar 

  26. Zhao, P. R.; Li, H. Y.; Bu, W. B. A forward vision for chemodynamic therapy: Issues and opportunities. Angew. Chem., Int. Ed. 2023, 62, e202210415.

    Article  CAS  Google Scholar 

  27. Zhao, P. R.; Jiang, Y. Q.; Tang, Z. M.; Li, Y. L.; Sun, B. X.; Wu, Y. L.; Wu, J. Y.; Liu, Y. Y.; Bu, W. B. Constructing electron levers in perovskite nanocrystals to regulate the local electron density for intensive chemodynamic therapy. Angew. Chem., Int. Ed. 2021, 60, 8905–8912.

    Article  CAS  Google Scholar 

  28. Zhang, H. L.; Chen, Y.; Hua, W.; Gu, W. J.; Zhuang, H. J.; Li, H. Y.; Jiang, X. W.; Mao, Y.; Liu, Y. Y.; Jin, D. Y. et al. Heterostructures with built-in electric fields for long-lasting chemodynamic therapy. Angew. Chem., Int. Ed. 2023, 62, e202300356.

    Article  CAS  Google Scholar 

  29. Yang, J. C.; Yao, H. L.; Guo, Y. D.; Yang, B. W.; Shi, J. L. Enhancing tumor catalytic therapy by co-catalysis. Angew. Chem., Int. Ed. 2022, 61, e202200480.

    Article  CAS  Google Scholar 

  30. Yang, L. X.; Wu, Y. N.; Wang, P. W.; Huang, K. J.; Su, W. C.; Shieh, D. B. Silver-coated zero-valent iron nanoparticles enhance cancer therapy in mice through lysosome-dependent dual programed cell death pathways: Triggering simultaneous apoptosis and autophagy only in cancerous cells. J. Mater. Chem. B 2020, 8, 4122–4131.

    Article  CAS  PubMed  Google Scholar 

  31. Dai, C.; Wang, C. M.; Hu, R. Z.; Lin, H.; Liu, Z.; Yu, L. D.; Chen, Y.; Zhang, B. Photonic/magnetic hyperthermia-synergistic nanocatalytic cancer therapy enabled by zero-valence iron nanocatalysts. Biomaterials 2019, 219, 119374.

    Article  CAS  PubMed  Google Scholar 

  32. Yu, H. H.; Lin, C. H.; Chen, Y. C.; Chen, H. H.; Lin, Y. J.; Lin, K. Y. A. Dopamine-modified zero-valent iron nanoparticles for dual-modality photothermal and photodynamic breast cancer therapy. ChemMedChem 2020, 15, 1645–1651.

    Article  CAS  PubMed  Google Scholar 

  33. Xi, J. Q.; Wei, G.; An, L. F.; Xu, Z. B.; Xu, Z. L.; Fan, L.; Gao, L. Z. Copper/carbon hybrid nanozyme: Tuning catalytic activity by the copper state for antibacterial therapy. Nano Lett. 2019, 19, 7645–7654.

    Article  CAS  PubMed  Google Scholar 

  34. Chang, P. H.; Chou, T. H.; Sahu, R. S.; Shih, Y. H. Chemical reduction-aided zerovalent copper nanoparticles for 2, 4-dichlorophenol removal. Appl. Nanosci. 2019, 9, 387–395.

    Article  CAS  Google Scholar 

  35. Wang, W. C.; Shi, X. T.; He, T. O.; Zhang, Z. R.; Yang, X. L.; Guo, Y. J.; Chong, B.; Zhang, W. M.; Jin, M. S. Tailoring amorphous PdCu nanostructures for efficient C-C cleavage in ethanol electrooxidation. Nano Lett. 2022, 22, 7028–7033.

    Article  CAS  PubMed  Google Scholar 

  36. Sahib, M. N.; Abdulameer, S. A.; Darwis, Y.; Peh, K. K.; Tan, Y. T. Solubilization of beclomethasone dipropionate in sterically stabilized phospholipid nanomicelles (SSMs): Physicochemical and in vitro evaluations. Drug. Des. Devel. Ther. 2012, 6, 29–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kastanek, F.; Spacilova, M.; Krystynik, P.; Dlaskova, M.; Solcova, O. Fenton reaction-unique but still mysterious. Processes 2023, 11, 432.

    Article  CAS  Google Scholar 

  38. Chang, M. Y.; Hou, Z. Y.; Wang, M.; Yang, C. Z.; Wang, R. F.; Li, F.; Liu, D. L.; Peng, T. L.; Li, C. X.; Lin, J. Single-atom pd nanozyme for ferroptosis-boosted mild-temperature photothermal therapy. Angew. Chem., Int. Ed. 2021, 60, 12971–12979.

    Article  CAS  Google Scholar 

  39. Ye, Z. C.; Li, Y.; Li, J. C.; Hu, X. Y.; Zheng, J. Y.; Zhang, G. X.; Xiang, S. J.; Zhu, T. B.; Guo, Z. D.; Chen, X. L. Pd@Ir-LOD multienzyme utilizing endogenous lactate consumption cooperates with photothermal for tumor therapy. Nano Res. 2024, 17, 270–281.

    Article  CAS  Google Scholar 

  40. Liu, C. H.; Lai, N. C.; Liou, S. C.; Chu, M. W.; Chen, C. H.; Yang, C. M. Deposition and thermal transformation of metal oxides in mesoporous SBA-15 silica with hydrophobic mesopores. Microporous Mesoporous Mater. 2013, 179, 40–47.

    Article  CAS  Google Scholar 

  41. Lin, B. P.; Chen, H. T.; Liang, D. Y.; Lin, W.; Qi, X. Y.; Liu, H. P.; Deng, X. Y. Acidic pH and high-H2O2 dual tumor microenvironment-responsive nanocatalytic graphene oxide for cancer selective therapy and recognition. ACS Appl. Mater. Interfaces 2019, 11, 11157–11166.

    Article  PubMed  Google Scholar 

  42. Chu, Z. Y.; Yang, J.; Zheng, W.; Sun, J. W.; Wang, W. N.; Qian, H. S. Recent advances on modulation of H2O2 in tumor microenvironment for enhanced cancer therapeutic efficacy. Coord. Chem. Rev. 2023, 481, 215049.

    Article  CAS  Google Scholar 

  43. Bogdanov, A.; Bogdanov, A.; Chubenko, V.; Volkov, N.; Moiseenko, F.; Moiseyenko, V. Tumor acidity: From hallmark of cancer to target of treatment. Front. Oncol. 2022, 12, 979154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bansal, A.; Simon, M. C. Glutathione metabolism in cancer progression and treatment resistance. J. Cell Biol. 2018, 217, 2291–2298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Niu, B. Y.; Liao, K. X.; Zhou, Y. X.; Wen, T.; Quan, G. L.; Pan, X.; Wu, C. B. Application of glutathione depletion in cancer therapy: Enhanced ROS-based therapy, ferroptosis, and chemotherapy. Biomaterials 2021, 277, 121110.

    Article  CAS  PubMed  Google Scholar 

  46. Yang, W. S.; SriRamaratnam, R.; Welsch, M. E.; Shimada, K.; Skouta, R.; Viswanathan, V. S.; Cheah, J. H.; Clemons, P. A.; Shamji, A. F.; Clish, C. B. et al. Regulation of ferroptotic cancer cell death by GPX4. Cell 2014, 156, 317–331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Dixon, S. J.; Lemberg, K. M.; Lamprecht, M. R.; Skouta, R.; Zaitsev, E. M.; Gleason, C. E.; Patel, D. N.; Bauer, A. J.; Cantley, A. M.; Yang, W. S. et al. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell 2012, 149, 1060–1072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Feng, W.; Liu, Z. L.; Xia, L. L.; Chen, M.; Dai, X. Y.; Huang, H.; Dong, C. H.; He, Y.; Chen, Y. A sonication-activated valence-variable sono-sensitizer/catalyst for autography inhibition/ferroptosis-induced tumor nanotherapy. Angew. Chem., Int. Ed. 2022, 61, e202212021.

    Article  CAS  Google Scholar 

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Acknowledgements

This work is financially supported by the National Key Research and Development Program of China (No. 2022YFB3804500), the National Natural Science Foundation of China (Nos. 52102354, 52102180, 52202353, and 52372273), and the Science and Technology Development Planning Project of Jilin Province (Nos. 20220101070JC, 20220508089RC, and 20210402046GH). All animals in this study were handled according to a protocol approved by the Institutional Animal Care and Use Committee of Jilin University.

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Authors and Affiliations

  1. State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Xinyang Li, Binbin Ding, Jing Li, Di Han, Hao Chen, Jia Tan, Qi Meng, Pan Zheng, Ping’an Ma & Jun Lin

  2. School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China

    Xinyang Li, Jing Li, Di Han, Hao Chen, Jia Tan, Qi Meng, Ping’an Ma & Jun Lin

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  1. Xinyang Li
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  2. Binbin Ding
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Correspondence to Binbin Ding, Ping’an Ma or Jun Lin.

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Electronic Supplementary Material: Valence-tailored copper-based nanoparticles for enhanced chemodynamic therapy through prolonged ROS generation and potentiated GSH depletion

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Li, X., Ding, B., Li, J. et al. Valence-tailored copper-based nanoparticles for enhanced chemodynamic therapy through prolonged ROS generation and potentiated GSH depletion. Nano Res. (2024). https://doi.org/10.1007/s12274-024-6552-2

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