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Sonodynamic therapy with immune modulatable two-dimensional coordination nanosheets for enhanced anti-tumor immunotherapy

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Abstract

Ultrasound with deep penetration depth and high security could be adopted in sonodynamic therapy (SDT) by activating sonosensitizers to generate cytotoxic reactive oxygen species (ROS). Herein, two-dimensional (2D) coordination nanosheets composed of Zn2+ and Tetrakis(4-carboxyphenyl) porphyrin (TCPP) are fabricated. While exhibiting greatly enhanced ultrasound-triggered ROS generation useful for noninvasive SDT, such Zn-TCPP 2D nanosheets show high loading capacity of oligodeoxynucleotides such as cytosine-phosphorothioate-guanine (CpG), which is a potent toll like receptor 9 (TLR9) agonist useful in activating immune responses. Highly effective SDT of primary tumors could release tumor-associated antigens, which working together with Zn-TCPP/CpG adjuvant nanosheets could function like whole-tumor-cell vaccines and trigger tumor-specific immune responses. Interestingly, ultrasound itself could strengthen anti-tumor immune responses by improving the tumor-infiltration of T cells and limiting regulatory T cells in the tumor microenvironment. Thus, SDT using Zn-TCPP/CpG nanosheets after destruction of primary tumors could induce potent antitumor immune responses to inhibit distant abscopal tumors without direct SDT treatment. Moreover, SDT with Zn-TCPP/CpG could trigger strong immunological memory effects to inhibit cancer recurrence after elimination of primary tumors. Therefore, the 2D coordination nanosheet may be a promising platform to deliver potent SDT-triggered immunotherapy for highly effective cancer treatment.

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References

  1. ter Haar, G. Therapeutic ultrasound. Eur. J. Ultrasound 1999, 9, 3–9.

    CAS  Google Scholar 

  2. Ferrara, K.; Pollard, R.; Borden, M. Ultrasound microbubble contrast agents: Fundamentals and application to gene and drug delivery. Annu. Rev. Biomed. Eng. 2007, 9, 415–447.

    CAS  Google Scholar 

  3. Mitragotri, S. Healing sound: The use of ultrasound in drug delivery and other therapeutic applications. Nat. Rev. Drug Discov. 2005, 4, 255–260.

    CAS  Google Scholar 

  4. Kost, J.; Mitragotri, S.; Gabbay, R. A.; Pishko, M.; Langer, R. Transdermal monitoring of glucose and other analytes using ultrasound. Nat. Med. 2000, 6, 347–350.

    CAS  Google Scholar 

  5. Tezel, A.; Paliwal, S.; Shen, Z. C.; Mitragotri, S. Low-frequency ultrasound as a transcutaneous immunization adjuvant. Vaccine 2005, 23, 3800–3807.

    CAS  Google Scholar 

  6. Schoellhammer, C. M.; Blankschtein, D.; Langer, R. Skin permeabilization for transdermal drug delivery: Recent advances and future prospects. Expert Opin. Drug Deliv. 2014, 11, 393–407.

    CAS  Google Scholar 

  7. Oberli, M. A.; Schoellhammer, C. M.; Langer, R.; Blankschtein, D. Ultrasound-enhanced transdermal delivery: Recent advances and future challenges. Ther. Deliv. 2014, 5, 843–857.

    CAS  Google Scholar 

  8. Peek, M. C. L.; Ahmed, M.; Scudder, J.; Baker, R.; Pinder, S. E.; Douek, M. High intensity focused ultrasound in the treatment of breast fibroadenomata: Results of the HIFU-F trial. Int. J. Hyperth. 2016, 32, 881–888.

    CAS  Google Scholar 

  9. Hijnen, N. M.; Heijman, E.; Köhler, M. O.; Ylihautala, M.; Ehnholm, G. J.; Simonetti, A. W.; Grüll, H. Tumour hyperthermia and ablation in rats using a clinical MR-HIFU system equipped with a dedicated small animal set-up. Int. J. Hyperth. 2012, 28, 141–155.

    Google Scholar 

  10. Trendowski, M. The promise of sonodynamic therapy. Cancer Metastasis Rev. 2014, 33, 143–160.

    CAS  Google Scholar 

  11. Costley, D.; McEwan, C.; Fowley, C.; McHale, A. P.; Atchison, J.; Nomikou, N.; Callan, J. F. Treating cancer with sonodynamic therapy: A review. Int. J. Hyperth. 2015, 31, 107–117.

    CAS  Google Scholar 

  12. McEwan, C.; Owen, J.; Stride, E.; Fowley, C.; Nesbitt, H.; Cochrane, D.; Coussios, C. C.; Borden, M.; Nomikou, N.; McHale, A. P. et al. Oxygen carrying microbubbles for enhanced sonodynamic therapy of hypoxic tumours. J. Control. Release 2015, 203, 51–56.

    CAS  Google Scholar 

  13. Gong, F.; Cheng, L.; Yang, N. L.; Betzer, O.; Feng, L. Z.; Zhou, Q.; Li, Y. G.; Chen, R. H.; Popovtzer, R.; Liu, Z. Ultrasmall oxygen-deficient bimetallic oxide MnWOX nanoparticles for depletion of endogenous GSH and enhanced sonodynamic cancer therapy. Adv. Mater. 2019, 31, 1900730.

    Google Scholar 

  14. Yumita, N.; Umemura, S. Sonodynamic therapy with photofrin II on AH130 solid tumor. Cancer Chemother. Pharmacol. 2003, 51, 174–178.

    CAS  Google Scholar 

  15. Rosenthal, I.; Sostaric, J. Z.; Riesz, P. Sonodynamic therapy-a review of the synergistic effects of drugs and ultrasound. Ultrason. Sonochem. 2004, 11, 349–363.

    CAS  Google Scholar 

  16. Su, X. M.; Wang, P.; Yang, S.; Zhang, K.; Liu, Q. H.; Wang, X. B. Sonodynamic therapy induces the interplay between apoptosis and autophagy in K562 cells through ROS. Int. J. Biochem. Cell Biol. 2015, 60, 82–92.

    CAS  Google Scholar 

  17. Cheng, J. L.; Sun, X.; Guo, S. Y.; Cao, W.; Chen, H. B.; **, Y. H.; Li, B.; Li, Q. N.; Wang, H.; Wang, Z. et al. Effects of 5-aminolevulinic acid-mediated sonodynamic therapy on macrophages. Int. J. Nanomedicine 2013, 8, 669–676.

    Google Scholar 

  18. Jiang, Y. Q.; Kou, J. Y.; Han, X. B.; Li, X. S.; Zhong, Z. Y.; Liu, Z. N.; Zheng, Y. H.; Tian, Y.; Yang, L. M. ROS-dependent activation of autophagy through the PI3K/Akt/mTOR pathway is induced by hydroxysafflor yellow a-sonodynamic therapy in THP-1 macrophages. Oxid. Med. Cell. Longev. 2017, 2017, 8519169.

    Google Scholar 

  19. Su, X. M.; Wang, P.; Wang, X. B.; Guo, L.; Li, S. L.; Liu, Q. H. Involvement of MAPK activation and ROS generation in human leukemia U937 cells undergoing apoptosis in response to sonodynamic therapy. Int. J. Radiat. Biol. 2013, 89, 915–927.

    CAS  Google Scholar 

  20. Zhang, Q. Y.; Bao, C. X.; Cai, X. J.; **, L. W.; Sun, L. L.; Lang, Y. H.; Li, L. B. Sonodynamic therapy-assisted immunotherapy: A novel modality for cancer treatment. Cancer Sci. 2018, 109, 1330–1345.

    CAS  Google Scholar 

  21. Zhao, H. J.; Zhao, B. B.; Li, L.; Ding, K. L.; **ao, H. F.; Zheng, C. X.; Sun, L. L.; Zhang, Z. Z.; Wang, L. Biomimetic decoy inhibits tumor growth and lung metastasis by reversing the drawbacks of sonodynamic therapy. Adv. Healthc. Mater. 2020, 9, 1901335.

    CAS  Google Scholar 

  22. Yue, W. W.; Chen, L.; Yu, L. D.; Zhou, B. G.; Yin, H. H.; Ren, W. W.; Liu, C.; Guo, L. H.; Zhang, Y. F.; Sun, L. P. et al. Checkpoint blockade and nanosonosensitizer-augmented noninvasive sonodynamic therapy combination reduces tumour growth and metastases in mice. Nat. Commun. 2019, 10, 2025.

    Google Scholar 

  23. Chen, Q.; Hu, Q. Y.; Dukhovlinova, E.; Chen, G. J.; Ahn, S.; Wang, C.; Ogunnaike, E. A.; Ligler, F. S.; Dotti, G.; Gu, Z. Photothermal therapy: Photothermal therapy promotes tumor infiltration and antitumor activity of CAR T cells (Adv. Mater. 23/2019). Adv. Mater. 2019, 31, 1970166.

    Google Scholar 

  24. Mehrad, H.; Farhoudi, M. Investigation of protoporphyrin IX-mediated sonodynamic therapy on intermediate stage atherosclerosis using a new computerized B-mode ultrasound analyzing method. Atherosclerosis 2016, 252, E192.

    Google Scholar 

  25. Yao, J. T.; Gao, W. W.; Wang, Y.; Wang, L.; Diabakte, K.; Li, J. Y.; Yang, J. M.; Jiang, Y. X.; Liu, Y. R.; Guo, S. Y. et al. Sonodynamic therapy suppresses neovascularization in atherosclerotic plaques via macrophage apoptosis-induced endothelial cell apoptosis. JACC Basic Transl. Sci. 2020, 5, 53–65.

    Google Scholar 

  26. Tang, C. H.; Lu, D. Y.; Tan, T. W.; Fu, W. M.; Yang, R. S. Ultrasound induces hypoxia-inducible factor-1 activation and inducible nitric-oxide synthase expression through the integrin/integrin-linked kinase/Akt/mammalian target of rapamycin pathway in osteoblasts. J. Biol. Chem. 2007, 282, 25406–25415.

    CAS  Google Scholar 

  27. Peng, Y.; Jia, L. M.; Wang, S.; Cao, W. W.; Zheng, J. H. Sonodynamic therapy improves anti-tumor immune effect by increasing the infiltration of CD8+ T cells and altering tumor blood vessels in murine B16F10 melanoma xenograft. Oncol. Rep. 2018, 40, 2163–2170.

    CAS  Google Scholar 

  28. Cheng, L.; Wang, X. W.; Gong, F.; Liu, T.; Liu, Z. 2D nanomaterials for cancer theranostic applications. Adv. Mater. 2020, 32, e1902333.

    Google Scholar 

  29. Zhang, H. Ultrathin two-dimensional nanomaterials. ACS Nano 2015, 9, 9451–9469.

    CAS  Google Scholar 

  30. Martín, C.; Kostarelos, K.; Prato, M.; Bianco, A. Biocompatibility and biodegradability of 2D materials: Graphene and beyond. Chem. Commun. 2019, 55, 5540–5546.

    Google Scholar 

  31. Manzeli, S.; Ovchinnikov, D.; Pasquier, D.; Yazyev, O. V.; Kis, A. 2D transition metal dichalcogenides. Nat. Rev. Mater. 2017, 2, 17033.

    CAS  Google Scholar 

  32. Naguib, M.; Mashtalir, O.; Carle, J.; Presser, V.; Lu, J.; Hultman, L.; Gogotsi, Y.; Barsoum, M. W. Two-dimensional transition metal carbides. ACS Nano 2012, 6, 1322–1331.

    CAS  Google Scholar 

  33. Lan, G. X.; Ni, K. Y.; Xu, R. Y.; Lu, K. D.; Lin, Z. K.; Chan, C.; Lin, W. B. Nanoscale metal-organic layers for deeply penetrating X-ray-induced photodynamic therapy. Angew. Chem. 2017, 129, 12270–12274.

    Google Scholar 

  34. Zhao, M. T.; Wang, Y. X.; Ma, Q. L.; Huang, Y.; Zhang, X.; **, J. F.; Zhang, Z. C.; Lu, Q. P.; Yu, Y. F.; Xu, H. et al. Ultrathin 2D metal-organic framework nanosheets. Adv. Mater. 2015, 27, 7372–7378.

    CAS  Google Scholar 

  35. Wan, S. S.; Cheng, Q.; Zeng, X.; Zhang, X. Z. A Mn(III)-sealed metal-organic framework nanosystem for redox-unlocked tumor theranostics. ACS Nano 2019, 13, 6561–6571.

    CAS  Google Scholar 

  36. Krieg, A. M. Antitumor applications of stimulating toll-like receptor 9 with CpG oligodeoxynucleotides. Curr. Oncol. Rep. 2004, 6, 88–95.

    Google Scholar 

  37. Akca, S.; Foroughi, A.; Frochtzwajg, D.; Postma, H. W. C. Competing interactions in DNA assembly on graphene. PLoS One 2011, 6, e18442.

    CAS  Google Scholar 

  38. Johnson, A. T. C.; Khamis, S. M.; Preti, G.; Kwak, J.; Gelperin, A. DNA-coated nanosensors for breath analysis. IEEE Sens. J. 2010, 10, 159–166.

    CAS  Google Scholar 

  39. Mignon, P.; Loverix, S.; Steyaert, J.; Geerlings, P. Influence of the π-π interaction on the hydrogen bonding capacity of stacked DNA/RNA bases. Nucleic Acids Res. 2005, 33, 1779–1789.

    CAS  Google Scholar 

  40. Zhu, C. F.; Zeng, Z. Y.; Li, H.; Li, F.; Fan, C. H.; Zhang, H. Single-layer MoS2-based nanoprobes for homogeneous detection of biomolecules. J. Am. Chem. Soc. 2013, 135, 5998–6001.

    CAS  Google Scholar 

  41. Zhu, W. J.; Yang, Y.; **, Q. T.; Chao, Y.; Tian, L. L.; Liu, J. J.; Dong, Z. L.; Liu, Z. Two-dimensional metal-organic-framework as a unique theranostic nano-platform for nuclear imaging and chemophotodynamic cancer therapy. Nano Res. 2019, 12, 1307–1312.

    CAS  Google Scholar 

  42. Ni, K. Y.; Luo, T. K.; Culbert, A.; Kaufmann, M.; Jiang, X. M.; Lin, W. B. Nanoscale metal-organic framework Co-delivers TLR-7 agonists and Anti-CD47 antibodies to modulate macrophages and orchestrate cancer immunotherapy. J. Am. Chem. Soc. 2020, 142, 12579–12584.

    CAS  Google Scholar 

  43. Lu, K. D.; He, C. B.; Lin, W. B. Nanoscale metal-organic framework for highly effective photodynamic therapy of resistant head and neck cancer. J. Am. Chem. Soc. 2014, 136, 16712–16715.

    CAS  Google Scholar 

  44. Rosenkranz, A. R.; Schmaldienst, S.; Stuhlmeier, K. M.; Chen, W. J.; Knapp, W.; Zlabinger, G. J. A microplate assay for the detection of oxidative products using 2′,7′-dichlorofluorescin-diacetate. J. Immunol. Methods 1992, 156, 39–45.

    CAS  Google Scholar 

  45. Campana, L.; Bosurgi, L.; Rovere-Querini, P. HMGB1: A two-headed signal regulating tumor progression and immunity. Curr. Opin. Immunol. 2008, 20, 518–523.

    CAS  Google Scholar 

  46. Obeid, M.; Tesniere, A.; Ghiringhelli, F.; Fimia, G. M.; Apetoh, L.; Perfettini, J. L.; Castedo, M.; Mignot, G.; Panaretakis, T.; Casares, N. et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat. Med. 2007, 13, 54–61.

    CAS  Google Scholar 

  47. Tesniere, A.; Apetoh, L.; Ghiringhelli, F.; Joza, N.; Panaretakis, T.; Kepp, O.; Schlemmer, F.; Zitvogel, L.; Kroemer, G. Immunogenic cancer cell death: A key-lock paradigm. Curr. Opin. Immunol. 2008, 20, 504–511.

    CAS  Google Scholar 

  48. **, Q.; Zhou, D. M.; Kan, Y. Y.; Ge, J.; Wu, Z. K.; Yu, R. Q.; Jiang, J. H. Highly sensitive and selective strategy for MicroRNA detection based on WS2 nanosheet mediated fluorescence quenching and duplex-specific nuclease signal amplification. Anal. Chem. 2014, 86, 1361–1365.

    CAS  Google Scholar 

  49. Ge, J.; Ou, E. C.; Yu, R. Q.; Chu, X. A novel aptameric nanobiosensor based on the self-assembled DNA-MoS2 nanosheet architecture for biomolecule detection. J. Mater. Chem. B 2014, 2, 625–628.

    CAS  Google Scholar 

  50. Zhang, H. Y.; Ruan, Y. J.; Lin, L.; Lin, M. G.; Zeng, X. X.; **, Z. M.; Fu, F. F. A turn-off fluorescent biosensor for the rapid and sensitive detection of uranyl ion based on molybdenum disulfide nanosheets and specific DNAzyme. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2015, 146, 1–6.

    CAS  Google Scholar 

  51. Müiz, C.; Steinman, R. M.; Fujii, S. Dendritic cell maturation by innate lymphocytes. J. Exp. Med. 2005, 202, 203–207.

    Google Scholar 

  52. Chen, Q.; Xu, L. G.; Liang, C.; Wang, C.; Peng, R.; Liu, Z. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nat. Commun. 2016, 7, 13193.

    CAS  Google Scholar 

  53. Semenza, G. L. Hypoxia-inducible factor 1 (HIF-1) pathway. Sci. STKE 2007, 407, cm8.

    Google Scholar 

  54. Schlesinger, M.; Bendas, G. Vascular cell adhesion molecule-1 (VCAM-1) — An increasing insight into its role in tumorigenicity and metastasis. Int. J. Cancer 2015, 136, 2504–2514.

    CAS  Google Scholar 

  55. Yoong, K. F.; McNab, G.; Hübscher, S. G.; Adams, D. H. Vascular adhesion protein-1 and ICAM-1 support the adhesion of tumor-infiltrating lymphocytes to tumor endothelium in human hepatocellular carcinoma. J. Immunol. 1998, 160, 3978–3988.

    CAS  Google Scholar 

  56. Chen, Q.; Chen, M. C.; Liu, Z. Local biomaterials-assisted cancer immunotherapy to trigger systemic antitumor responses. Chem. Soc. Rev. 2019, 48, 5506–5526.

    CAS  Google Scholar 

  57. Nam, J.; Son, S.; Ochyl, L. J.; Kuai, R.; Schwendeman, A.; Moon, J. J. Chemo-photothermal therapy combination elicits anti-tumor immunity against advanced metastatic cancer. Nat. Commun. 2018, 9, 1074.

    Google Scholar 

  58. Chen, Q.; Xu, L. G.; Chen, J. W.; Yang, Z. J.; Liang, C.; Yang, Y.; Liu, Z. Tumor vasculature normalization by orally fed erlotinib to modulate the tumor microenvironment for enhanced cancer nanomedicine and immunotherapy. Biomaterials 2017, 148, 69–80.

    CAS  Google Scholar 

  59. Chao, Y.; Xu, L. G.; Liang, C.; Feng, L. Z.; Xu, J.; Dong, Z. L.; Tian, L. L.; Yi, X.; Yang, K.; Liu, Z. Combined local immunostimulatory radioisotope therapy and systemic immune checkpoint blockade imparts potent antitumour responses. Nat. Biomed. Eng. 2018, 2, 611–621.

    CAS  Google Scholar 

  60. Chen, Q.; Chen, J. W.; Yang, Z. J.; Xu, J.; Xu, L. G.; Liang, C.; Han, X.; Liu, Z. Nanoparticle-enhanced radiotherapy to trigger robust cancer immunotherapy. Adv. Mater. 2019, 31, 1802228.

    Google Scholar 

  61. Chao, Y.; Chen, G. B.; Liang, C.; Xu, J.; Dong, Z. L.; Han, X.; Wang, C.; Liu, Z. Iron nanoparticles for low-power local magnetic hyperthermia in combination with immune checkpoint blockade for systemic antitumor therapy. Nano Lett. 2019, 19, 4287–4296.

    CAS  Google Scholar 

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Acknowledgements

This article was partially supported by the National Research Programs of China (No. 2016YFA0201200), the National Natural Science Foundation of China (Nos. 91959104, 21927803, 51903182, and 51525203,), the Natural Science Foundation of Jiangsu Province (No. BK20190826), Collaborative Innovation Center of Suzhou Nano Science and Technology, and the 111 Program from the Ministry of Education of China.

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  1. Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, 215123, China

    Wenjun Zhu, Qian Chen, Qiutong **, Yu Chao, Lele Sun, **ao Han, Jun Xu, Longlong Tian, **glei Zhang & Zhuang Liu

  2. State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China

    Teng Liu

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  1. Wenjun Zhu
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  2. Qian Chen
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Correspondence to Qian Chen or Zhuang Liu.

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Sonodynamic therapy with immune modulatable two-dimensional coordination nanosheets for enhanced anti-tumor immunotherapy

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Zhu, W., Chen, Q., **, Q. et al. Sonodynamic therapy with immune modulatable two-dimensional coordination nanosheets for enhanced anti-tumor immunotherapy. Nano Res. 14, 212–221 (2021). https://doi.org/10.1007/s12274-020-3070-8

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