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Harnessing chlorin e6 loaded by functionalized iron oxide nanoparticles linked with glucose for target photodynamic therapy and improving of the immunogenicity of lung cancer

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Non-small-cell lung cancer (NSCLC) is the most common malignant lung tumor and is difficult to be eradicated due to its immunosuppressive microenvironment. Chlorin e6 (Ce6)-mediated photodynamic therapy (PDT) could improve immunogenicity while destroying malignant tumor cells. However, the clinic application of Ce6-mediated PDT is limited by Ce6’s poor water solubility and insufficient accumulation in lung cancer. To address this issue, Ce6 was loaded onto functionalized iron oxide nanoparticles linked with glucose to improve the distribution of Ce6 in lung cancer.

Materials and results

The results of transmission electron microscopy (TEM), UV–Vis spectrophotometry, dynamic light scattering and near-infrared (NIR) spectroscopy confirmed the successful preparation of the composites. Confocal and flow cytometry showed IO–PG–GLU–Ce6 significantly enhanced the uptake of Ce6 by lung cancer cells and produced more reactive oxygen species (ROS) under NIR light irradiation. In addition, the detection of cell viability, proliferation and apoptosis indicated IO–PG–GLU–Ce6 achieved stronger photo-toxicity to lung cancer cells. Moreover, IO–PG–GLU–Ce6 treatment effectively damaged the DNA of lung cancer cells and thereby activated STING, up-regulated the expression of IFN-β, HMGB1 and HSP90, indicating augmented immunogenicity of lung cancer cells. Further results of in vivo, organ imaging and tissue fluorescence sections demonstrated IO–PG–GLU–Ce6 significantly improved the distribution of Ce6 in tumor tissues of lung cancer-bearing mice as well. Finally, the findings of in vivo study and immunohistochemistry confirmed the better efficacy of IO–PG–GLU–Ce6. HE staining results of vital organs suggested that the composites were less toxic.

Conclusion

In conclusion, Ce6 loaded by functionalized iron oxide nanoparticles linked with glucose exhibited both target photodynamic efficacy and the ability to enhance its immunogenicity in lung cancer. This study provides a promising strategy for augment of the targeting delivery of Ce6 and its mediated photodynamic and immunotherapy.

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Acknowledgements

This research was supported by the Hubei Provincial Natural Science Foundation (2020CFB152), Cultivating Project for Young Scholar at Hubei University of Medicine (2020QDJZR002, 2019QDJZR02), Innovative Research Program for Graduates of Hubei University of Medicine (YC2021016), National Training Program of Innovation and Entrepreneurship for Undergraduates (202110929010, 202113249001).

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Author notes

  1. Ting-Ting Yu and Xing-Chun Peng have contributed equally to this article.

Authors and Affiliations

  1. School of Basic Medical Sciences, Hubei University of Medicine, Renmin road No. 30, Shiyan, 442000, Hubei, China

    Ting-Ting Yu, Xing-Chun Peng, Ning Han, Qi-Rui Li, Liu-Gen Li, Xiang Xu, Qian-Li Ma, Bin Liu, Jue Wang & Tong-Fei Li

  2. Department of Respiratory, Taihe Hospital of Shiyan, Hubei University of Medicine, Renmin road No. 30, Shiyan, 442000, Hubei, China

    Ting-Ting Yu, Xing-Chun Peng, Mei-Fang Wang, Ning Han, Qi-Rui Li, Liu-Gen Li, Xiang Xu & Tong-Fei Li

  3. Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Renmin road No. 30, Shiyan, 442000, Hubei, China

    Ting-Ting Yu, Mei-Fang Wang, Ning Han, Qi-Rui Li, Xiang Xu & Tong-Fei Li

  4. Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Donghu Avenue No.185, Wuhan, 430072, China

    Hua-Zhen Xu & Xiao Chen

  5. Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China

    Hua-Zhen Xu & Xiao Chen

  6. 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, Jiangsu, China

    Li Zhao

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  1. Ting-Ting Yu
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Yu, TT., Peng, XC., Wang, MF. et al. Harnessing chlorin e6 loaded by functionalized iron oxide nanoparticles linked with glucose for target photodynamic therapy and improving of the immunogenicity of lung cancer. J Cancer Res Clin Oncol 148, 867–879 (2022). https://doi.org/10.1007/s00432-021-03879-x

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