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

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. 2022 Apr;148(4):867-879. doi: 10.1007/s00432-021-03879-x.
Ting-Ting Yu  # 1 2 3,  Xing-Chun Peng  # 1 2,  Mei-Fang Wang 2 3,  Ning Han 1 2 3,  Hua-Zhen Xu 4 5,  Qi-Rui Li 1 2 3,  Liu-Gen Li 1 2,  Xiang Xu 1 2 3,  Qian-Li Ma 1,  Bin Liu 1,  Jue Wang 1,  Li Zhao 6,  Xiao Chen 7 8,  Tong-Fei Li 9 10 11
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Hubei University of Medicine, Renmin road No. 30, Shiyan, 442000, Hubei, China.
  • 2 Department of Respiratory, Taihe Hospital of Shiyan, Hubei University of Medicine, Renmin road No. 30, Shiyan, 442000, Hubei, China.
  • 3 Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Renmin road No. 30, Shiyan, 442000, Hubei, China.
  • 4 Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Donghu Avenue No.185, Wuhan, 430072, China.
  • 5 Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China.
  • 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.
  • 7 Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Donghu Avenue No.185, Wuhan, 430072, China. chen-xiao-1976@hotmail.com.
  • 8 Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. chen-xiao-1976@hotmail.com.
  • 9 School of Basic Medical Sciences, Hubei University of Medicine, Renmin road No. 30, Shiyan, 442000, Hubei, China. litongfeihappy@163.com.
  • 10 Department of Respiratory, Taihe Hospital of Shiyan, Hubei University of Medicine, Renmin road No. 30, Shiyan, 442000, Hubei, China. litongfeihappy@163.com.
  • 11 Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Renmin road No. 30, Shiyan, 442000, Hubei, China. litongfeihappy@163.com.
  • # Contributed equally.
PMID: 34997349 DOI: 10.1007/s00432-021-03879-x
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.

Keywords

Chlorin e6; Glucose; Immunogenicity; Lung cancer; Nano-iron oxide; Photodynamic effect.

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