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A novel two-dimensional nanoheterojunction via facilitating electron—hole pairs separation for synergistic tumor phototherapy and immunotherapy

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Abstract

Nanomaterial-mediated phototherapy in tumor treatment has been developed rapidly in the past few years due to its noninvasive character. However, the low energy conversion efficiency and high recombination rate of the photo-triggered electron-hole pairs of single nano-agent limit the phototherapy efficiency. Herein, we constructed a novel two-dimensional nanoheterojunction MoS2-Ti3C2 (MT), which allowed a high photothermal conversion efficiency (59.1%) as well as an effective separation of photo-triggered electron-hole pairs for reactive oxygen species (ROS) generation under single 808 nm laser irradiation. Upon the modification of the mitochondrial targeted molecule (3-proxycarboxylic) triphenyl phosphine bromide (TPP) and 4T1 cell membrane, m@MoS2-Ti3C2/TPP (m@MTT) could effectively target to the tumor cell and further locate to the mitochondria to amplify tumor-specific oxidative stress, which not merely effectively inhibits the local tumor growth but also induces tumor immunogenic cell death (ICD) for activating antitumor immune response. Additionally, cytosine guanine dinucleotide (CPG), as a Toll-like receptor 9 (TLR9) agonist, was further introduced to the system to boost adaptive immune responses, resulting in improved level of cytotoxic T cells as well as a decrease in the number of regulatory T cells. In vivo antitumor mechanism studies demonstrated that not only the primary and distant tumors in 4T1 bearing-tumor mice model were significantly inhibited, but also the lung metastasis of tumor was effectively suppressed. Therefore, this work revealed the ROS generation mechanism of MT nanoheterojunction and provided a novel strategy to fabricate a biomedically applicable MT nanoheterojunction for tumor treatment.

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References

  1. Siegel, R. L.; Miller, K. D.; Fuchs, H. E.; Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin. 2022, 72, 7–33.

    Google Scholar 

  2. Xia, C. F.; Dong, X. S.; Li, H.; Cao, M. M.; Sun, D. Q.; He, S. Y.; Yang, F.; Yan, X. X.; Zhang, S. L.; Li, N. et al. Cancer statistics in China and United States, 2022: Profiles, trends, and determinants. Chin. Med. J. 2022, 135, 584–590.

    Google Scholar 

  3. Liu, Y. Y.; Meng, X. F.; Bu, W. B. Upconversion-based photodynamic cancer therapy. Coord. Chem. Rev. 2019, 379, 82–98.

    CAS  Google Scholar 

  4. Min, F. L.; Zhang, H.; Li, W. J. Current status of tumor radiogenic therapy. World J. Gastroenterol. 2005, 11, 3014–3019.

    CAS  Google Scholar 

  5. Wang, J.; Wu, X.; Shen, P.; Wang, J.; Shen, Y. D.; Shen, Y.; Webster, T. J.; Deng, J. J. Applications of inorganic nanomaterials in photothermal therapy based on combinational cancer treatment. Int. J. Nanomed. 2020, 15, 1903–1914.

    Google Scholar 

  6. Li, Z.; Xiao, C.; Yong, T. Y.; Li, Z. F.; Gan, L.; Yang, X. L. Influence of nanomedicine mechanical properties on tumor targeting delivery. Chem. Soc. Rev. 2020, 49, 2273–2290.

    CAS  Google Scholar 

  7. Norouzi, M.; Amerian, M.; Amerian, M.; Atyabi, F. Clinical applications of nanomedicine in cancer therapy. Drug Discovery Today 2020, 25, 107–125.

    CAS  Google Scholar 

  8. Wolfram, J.; Ferrari, M. Clinical cancer nanomedicine. Nano Today 2019, 25, 85–98.

    CAS  Google Scholar 

  9. Yang, B. W.; Chen, Y.; Shi, J. L. Reactive oxygen species (ROS)-based nanomedicine. Chem. Rev. 2019, 119, 4881–4985.

    CAS  Google Scholar 

  10. Rocha, U.; Jacinto, C.; Kumar, K. U.; López, F. J.; Bravo, D.; Solé, J. G.; Jaque, D. Real-time deep-tissue thermal sensing with sub-degree resolution by thermally improved Nd3+ LaF3 multifunctional nanoparticles. J. Lumin. 2016, 175, 149–157.

    CAS  Google Scholar 

  11. Yang, B. W.; Chen, Y.; Shi, J. L. Tumor-specific chemotherapy by nanomedicine-enabled differential stress sensitization. Angew. Chem., Int. Ed. 2020, 59, 9693–9701.

    CAS  Google Scholar 

  12. Zheng, D. Y.; Yu, P. W.; Wei, Z. W.; Zhong, C.; Wu, M.; Liu, X. L. RBC membrane camouflaged semiconducting polymer nanoparticles for near-infrared photoacoustic imaging and photothermal therapy. Nano-Micro Lett. 2020, 12, 94.

    CAS  Google Scholar 

  13. Zhao, L. Z.; Li, J. Y.; Su, Y. Q.; Yang, L. Q.; Chen, L.; Qiang, L.; Wang, Y. J.; Xiang, H. J.; Tham, H. P.; Peng, J. J. et al. MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy. Sci. Adv. 2020, 6, eaaz0575.

    CAS  Google Scholar 

  14. Blanchard, P.; Biau, J.; Huguet, F.; Racadot, S.; Berthold, C.; Wong-Hee-Kam, S.; Biston, M. C.; Maingon, P. Radiotherapy for nasopharyngeal cancer. Cancer/Radiothér. 2022, 26, 168–173.

    CAS  Google Scholar 

  15. Chargari, C.; Peignaux, K.; Escande, A.; Renard, S.; Lafond, C.; Petit, A.; Hannoun-Lévi, J. M.; Durdux, C.; Haie-Méder, C. Radiotherapy for endometrial cancer. Cancer/Radiothér. 2022, 26, 309–314.

    CAS  Google Scholar 

  16. Zhang, D. Y.; Liu, H. K.; Younis, M. R.; Lei, S.; Chen, Y. Z.; Huang, P.; Lin, J. In-situ TiO2−x decoration of titanium carbide MXene for photo/sono-responsive antitumor theranostics. J. Nanobiotechnol. 2022, 20, 53.

    CAS  Google Scholar 

  17. Shao, J. D.; Zhang, J.; Jiang, C.; Lin, J.; Huang, P. Biodegradable titanium nitride MXene quantum dots for cancer phototheranostics in NIR-I/II biowindows. Chem. Eng. J. 2020, 400, 126009.

    CAS  Google Scholar 

  18. Vendrely, V.; Del Campo, E. R.; Modesto, A.; Jolnerowski, M.; Meillan, N.; Chiavassa, S.; Serre, A. A.; Gérard, J. P.; Créhanges, G.; Huguet, F. et al. Rectal cancer radiotherapy. Cancer/Radiothér. 2022, 26, 272–278.

    CAS  Google Scholar 

  19. Cusack, J. C.; Tanabe, K. K. Cancer gene therapy. Surg. Oncol. Clin. North Am. 1998, 7, 421–469.

    Google Scholar 

  20. Huang, K.; Li, Z. J.; Lin, J.; Han, G.; Huang, P. Two-dimensional transition metal carbides and nitrides (MXenes) for biomedical applications. Chem. Soc. Rev. 2018, 47, 5109–5124.

    CAS  Google Scholar 

  21. Geng, B. J.; Xu, S.; Shen, L. X.; Fang, F. L.; Shi, W. Y.; Pan, D. Y. Multifunctional carbon dot/MXene heterojunctions for alleviation of tumor hypoxia and enhanced sonodynamic therapy. Carbon 2021, 179, 493–504.

    CAS  Google Scholar 

  22. Mathis, T. S.; Maleski, K.; Goad, A.; Sarycheva, A.; Anayee, M.; Foucher, A. C.; Hantanasirisakul, K.; Shuck, C. E.; Stach, E. A.; Gogotsi, Y. Modified MAX phase synthesis for environmentally stable and highly conductive Ti3C2 MXene. Acs Nano 2021, 15, 6420–6429.

    CAS  Google Scholar 

  23. Zhang, Y. Y.; Cheng, Y. R.; Yang, F.; Yuan, Z. P.; Wei, W.; Lu, H. T.; Dong, H. F.; Zhang, X. J. Near-infrared triggered Ti3C2/g-C3N4 heterostructure for mitochondria-targeting multimode photodynamic therapy combined photothermal therapy. Nano Today 2020, 34, 100919.

    CAS  Google Scholar 

  24. Liu, G. Y.; Zou, J. H.; Tang, Q. Y.; Yang, X. Y.; Zhang, Y. W.; Zhang, Q.; Huang, W.; Chen, P.; Shao, J. J.; Dong, X. C. Surface modified Ti3C2 MXene nanosheets for tumor targeting photothermal/photodynamic/chemo synergistic therapy. ACS Appl. Mater. Interfaces 2017, 9, 40077–40086.

    CAS  Google Scholar 

  25. Tang, W. T.; Dong, Z. L.; Zhang, R.; Yi, X.; Yang, K.; Jin, M. L.; Yuan, C.; Xiao, Z. D.; Liu, Z.; Cheng, L. Multifunctional two-dimensional core-shell MXene@gold nanocomposites for enhanced photo-radio combined therapy in the second biological window. ACS Nano 2019, 13, 284–294.

    CAS  Google Scholar 

  26. Attanayake, N. H.; Abeyweera, S. C.; Thenuwara, A. C.; Anasori, B.; Gogotsi, Y.; Sun, Y. G.; Strongin, D. R. Vertically aligned MoS2 on Ti3C2 (MXene) as an improved HER catalyst. J. Mater. Chem. A 2018, 6, 16882–16889.

    CAS  Google Scholar 

  27. Liu, Y. X.; Tian, Y.; Han, Q. Y.; Yin, J.; Zhang, J. C.; Yu, Y.; Yang, W. Z.; Deng, Y. Synergism of 2D/1D MXene/cobalt nanowire heterojunctions for boosted photo-activated antibacterial application. Chem. Eng. J. 2021, 410, 128209.

    CAS  Google Scholar 

  28. Cai, T.; Wang, L. L.; Liu, Y. T.; Zhang, S. Q.; Dong, W. Y.; Chen, H.; Yi, X. Y.; Yuan, J. L.; Xia, X. N.; Liu, C. B. et al. Ag3PO4/Ti3C2 MXene interface materials as a Schottky catalyst with enhanced photocatalytic activities and anti-photocorrosion performance. Appl. Catal. B:Environ. 2018, 239, 545–554.

    CAS  Google Scholar 

  29. Ekspong, J.; Sandström, R.; Rajukumar, L. P.; Terrones, M.; Wågberg, T.; Gracia-Espino, E. Stable sulfur-intercalated 1T’ MoS2 on graphitic nanoribbons as hydrogen evolution electrocatalyst. Adv. Funct. Mater. 2018, 28, 1802744.

    Google Scholar 

  30. Ekspong, J.; Sharifi, T.; Shchukarev, A.; Klechikov, A.; Wågberg, T.; Gracia-Espino, E. Stabilizing active edge sites in semicrystalline molybdenum sulfide by anchorage on nitrogen-doped carbon nanotubes for hydrogen evolution reaction. Adv. Funct. Mater. 2016, 26, 6766–6776.

    CAS  Google Scholar 

  31. Ting, L. R. L.; Deng, Y. L.; Ma, L.; Zhang, Y. J.; Peterson, A. A.; Yeo, B. S. Catalytic activities of sulfur atoms in amorphous molybdenum sulfide for the electrochemical hydrogen evolution reaction. ACS Catal. 2016, 6, 861–867.

    CAS  Google Scholar 

  32. Yan, J.; Ren, C. E.; Maleski, K.; Hatter, C. B.; Anasori, B.; Urbankowski, P.; Sarycheva, A.; Gogotsi, Y. Flexible MXene/graphene films for ultrafast supercapacitors with outstanding volumetric capacitance. Adv. Funct. Mater. 2017, 27, 1701264.

    Google Scholar 

  33. Wu, X. H.; Wang, Z. Y.; Yu, M. Z.; Xiu, L. Y.; Qiu, J. S. Stabilizing the MXenes by carbon nanoplating for developing hierarchical nanohybrids with efficient lithium storage and hydrogen evolution capability. Adv. Mater. 2017, 29, 1607017.

    Google Scholar 

  34. Wang, J.; Fang, W. H.; Hu, Y.; Zhang, Y. H.; Dang, J. Q.; Wu, Y.; Zhao, H.; Li, Z. X. Different phases of few-layer MoS2 and their silver/gold nanocomposites for efficient hydrogen evolution reaction. Catal. Sci. Technol. 2020, 10, 154–163.

    Google Scholar 

  35. Xia, Z. H.; Tao, Y. Q.; Pan, Z. G.; Shen, X. D. Enhanced photocatalytic performance and stability of 1T MoS2 transformed from 2H MoS2 via Li intercalation. Results Phys. 2019, 12, 2218–2224.

    Google Scholar 

  36. Wang, X.; Li, H.; Li, H.; Lin, S.; Ding, W.; Zhu, X. G.; Sheng, Z. G.; Wang, H.; Zhu, X. B.; Sun, Y. P. 2D/2D 1T-MoS2/Ti3C2 MXene heterostructure with excellent supercapacitor performance. Adv. Funct. Mater. 2020, 30, 0190302.

    CAS  Google Scholar 

  37. Zhang, X. G.; Cheng, L. L.; Lu, Y.; Tang, J. J.; Lv, Q. J.; Chen, X. M.; Chen, Y.; Liu, J. A MXene-based bionic cascaded-enzyme nanoreactor for tumor phototherapy/enzyme dynamic therapy and hypoxia-activated chemotherapy. Nano-Micro Lett. 2022, 14, 22.

    Google Scholar 

  38. Pang, B.; Yang, H. R.; Wang, L. Y.; Chen, J. Q.; Jin, L. H.; Shen, B. J. Aptamer modified MoS2 nanosheets application in targeted photothermal therapy for breast cancer. Colloids Surf. A: Physicochem. Eng. Aspects 2021, 608, 125506.

    CAS  Google Scholar 

  39. Yang, Z. P.; Fu, X. L.; Ma, D. C.; Wang, Y. L.; Peng, L. M.; Shi, J. C.; Sun, J. Y.; Gan, X. Q.; Deng, Y.; Yang, W. Z. Growth factor-decorated Ti3C2 MXene/MoS2 2D bio-heterojunctions with quad-channel photonic disinfection for effective regeneration of bacteria-invaded cutaneous tissue. Small 2021, 17, 2103993.

    CAS  Google Scholar 

  40. Shi, W. L.; Hao, C. C.; Fu, Y. M.; Guo, F.; Tang, Y. B.; Yan, X. Enhancement of synergistic effect photocatalytic/persulfate activation for degradation of antibiotics by the combination of photo-induced electrons and carbon dots. Chem. Eng. J. 2022, 433, 133741.

    CAS  Google Scholar 

  41. Xia, D. H.; Wang, W. J.; Yin, R.; Jiang, Z. F.; An, T. C.; Li, G. Y.; Zhao, H. J.; Wong, P. K. Enhanced photocatalytic inactivation of Escherichia coli by a novel Z-scheme g-C3N4/m-Bi2O4 hybrid photocatalyst under visible light: The role of reactive oxygen species. Appl. Catal. B:Environ. 2017, 214, 23–33.

    CAS  Google Scholar 

  42. Onodera, Y.; Nam, J. M.; Horikawa, M.; Shirato, H.; Sabe, H. Arf6-driven cell invasion is intrinsically linked to TRAK1-mediated mitochondrial anterograde trafficking to avoid oxidative catastrophe. Nat. Commun. 2018, 9, 2682.

    Google Scholar 

  43. Zhai, Y. H.; Liu, M.; Yang, T.; Luo, J.; Wei, C. G.; Shen, J. K.; Song, X.; Ke, H. T.; Sun, P.; Guo, M. et al. Self-activated arsenic manganite nanohybrids for visible and synergistic thermo/immunoarsenotherapy. J. Control. Release 2022, 350, 761–776.

    CAS  Google Scholar 

  44. Chen, Z. K.; Liu, L. L.; Liang, R. J.; Luo, Z. Y.; He, H. M.; Wu, Z. H.; Tian, H.; Zheng, M. B.; Ma, Y. F.; Cai, L. T. Bioinspired hybrid protein oxygen nanocarrier amplified photodynamic therapy for eliciting anti-tumor immunity and abscopal effect. ACS Nano 2018, 12, 8633–8645.

    CAS  Google Scholar 

  45. Zhou, S. Y.; Li, D. D.; Lee, C.; Xie, J. Nanoparticle phototherapy in the era of cancer immunotherapy. Trends Chem. 2020, 2, 1082–1095.

    CAS  Google Scholar 

  46. Jahrsdorfer, B.; Weiner, G. J. CpG oligodeoxynucleotides as immunotherapy in cancer. Update Cancer Ther. 2008, 3, 27–32.

    Google Scholar 

  47. Yang, N.; Cao, C. Y.; Li, H.; Hong, Y.; Cai, Y.; Song, X. J.; Wang, W. J.; Mou, X. Z.; Dong, X. C. Polymer-based therapeutic nanoagents for photothermal-enhanced combination cancer therapy. Small Struct. 2021, 2, 2100110.

    CAS  Google Scholar 

  48. Jiang, Z. J.; Li, T. Y.; Cheng, H.; Zhang, F.; Yang, X. Y.; Wang, S. H.; Zhou, J. P.; Ding, Y. Nanomedicine potentiates mild photothermal therapy for tumor ablation. Asian J. Pharm. Sci. 2021, 16, 738–761.

    Google Scholar 

  49. Powell, E.; Piwnica-Worms, D.; Piwnica-Worms, H. Contribution of p53 to metastasis. Cancer Discov. 2014, 4, 405–414.

    CAS  Google Scholar 

  50. Smith, H. A.; Kang, Y. B. The metastasis-promoting roles of tumor-associated immune cells. J. Mol. Med. 2013, 91, 411–429.

    CAS  Google Scholar 

  51. Wortzel, I.; Dror, S.; Kenific, C. M.; Lyden, D. Exosome-mediated metastasis: Communication from a distance. Dev. Cell 2019, 49, 347–360.

    CAS  Google Scholar 

  52. Qiu, X. Y.; Qu, Y.; Guo, B. B.; Zheng, H.; Meng, F. H.; Zhong, Z. Y. Micellar paclitaxel boosts ICD and chemo-immunotherapy of metastatic triple negative breast cancer. J. Control. Release 2022, 341, 498–510.

    CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 51773231), Shenzhen Science and Technology Project (No. JCYJ20190807160801664), and the Foundation of Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument (No. 2020B1212060077).

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  1. Xiaoge Zhang and Xiaomei Chen contributed equally to this work.

Authors and Affiliations

  1. School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, China

    Xiaoge Zhang, Xiaomei Chen, Peng Zhang, Meiting Li, Miao Feng, Yaqian Zhang, Lili Cheng, Junjie Tang, Langtao Xu, Yadong Liu, Zhuoyin Liu, Zhong Cao & Jie Liu

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  1. Xiaoge Zhang
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  2. Xiaomei Chen
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  3. Peng Zhang
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  13. Jie Liu
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Correspondence to Zhong Cao or Jie Liu.

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A novel two-dimensional nanoheterojunction via facilitating electron-hole pairs separation for synergistic tumor phototherapy and immunotherapy

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Zhang, X., Chen, X., Zhang, P. et al. A novel two-dimensional nanoheterojunction via facilitating electron—hole pairs separation for synergistic tumor phototherapy and immunotherapy. Nano Res. 16, 7148–7163 (2023). https://doi.org/10.1007/s12274-022-5313-3

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