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Near-infrared light switching nitric oxide nanogenerator with “linkage mechanism” for tumor targeting multimodal synergistic therapy

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Abstract

Gaseous therapy based on nitric oxide (NO), as a potential anti-tumor treatment strategy, has attracted great attention, but the targeted and controlled gas release in the tumor site still remains a challenge. In addressing these difficulties, a near-infrared (NIR) light-triggered NO release nanogenerator with a “linkage mechanism” was designed on the basis of sodium nitroprusside-doped mesoporous Prussian blue nanoparticles, in which the outer structure was modified with pH-sensitive gatekeeper chitosan and tumor-targeting agent folic acid. The “linkage mechanism” can achieve precise release of NO under the control of photothermal effect at tumor site, which can couple photothermal therapy and gas therapy to address the premature release of gas during transportation. Meanwhile, the amount of released gas can be controlled by adjusting the irradiation time and laser intensity. Furthermore, as-fabricated nanocomposites hold high photothermal conversion efficiency under NIR laser irradiation, resulting in the on-demand release of NO and chemotherapy drugs. The released NO can inhibit the expression of hypoxia-inducible factor α (HIF-1α) and alleviate the hypoxic tumor microenvironment, thereby enhancing the efficacy of chemotherapy. Moreover, in vitro and in vivo experiments exhibited remarkable antitumor efficiency, and the synergistic gas/chemo/photothermal therapy of deep tumors was achieved. These findings indicate an effective strategy to stimulate further the development of deep tumor therapy, which may provide new insights into other NO-related medical applications.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21908059), the China Postdoctoral Science Foundation (2019M651419), the Shanghai Sailing Program (19YF1410900, 21YF1451700), the Natural Science Foundation of Shanghai (22ZR1415400), the Fundamental Research Funds for the Central Universities (22221818014), the Shanghai Post-doctoral Excellence Program (2018011), the Foundation of State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences (GZKF202031) and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering, Biomedical Nanotechnology Center, School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China

    Wei Zhang, Qize Xuan, Qi Zhang, Tong Wang & Chao Chen

  2. Institute for Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China

    Chen Wang, Hui Li & Chao Chen

  3. Department of Bioproducts and Biosystems Engineering, University of Minnesota, St Paul, MN, 55108, USA

    Ping Wang

Authors
  1. Wei Zhang
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  2. Qize Xuan
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  3. Qi Zhang
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  4. Tong Wang
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  5. Chen Wang
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  6. Hui Li
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  7. Chao Chen
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  8. Ping Wang
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Correspondence to Hui Li or Chao Chen.

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Conflict of interest The authors declare no conflict of interest.

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Supporting information The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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11426_2022_1434_MOESM1_ESM.pdf

Near-Infrared Light Switching Nitric Oxide Nanogenerator with “Linkage Mechanism” for Tumor Targeting Multimodal Synergistic Therapy

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Zhang, W., Xuan, Q., Zhang, Q. et al. Near-infrared light switching nitric oxide nanogenerator with “linkage mechanism” for tumor targeting multimodal synergistic therapy. Sci. China Chem. 66, 586–600 (2023). https://doi.org/10.1007/s11426-022-1434-0

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