Establishment of NaLuF<sub>4</sub>:15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

Yi Tian; Zhiguang Fu; Xiaosheng Zhu; Chunjing Zhan; Jinwei Hu; Li Fan; Chaojun Song; Qian Yang; Yu Wang; Mei Shi

doi:10.1007/s12613-023-2717-3

Volume 31 Issue 3

Mar. 2024

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Article Navigation > International Journal of Minerals, Metallurgy and Materials > 2024 > 31(3): 599-610

Yi Tian, Zhiguang Fu, Xiaosheng Zhu, Chunjing Zhan, Jinwei Hu, Li Fan, Chaojun Song, Qian Yang, Yu Wang, and Mei Shi, Establishment of NaLuF₄:15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy, Int. J. Miner. Metall. Mater., 31(2024), No. 3, pp. 599-610. https://doi.org/10.1007/s12613-023-2717-3

Cite this article as:

Yi Tian, Zhiguang Fu, Xiaosheng Zhu, Chunjing Zhan, Jinwei Hu, Li Fan, Chaojun Song, Qian Yang, Yu Wang, and Mei Shi, Establishment of NaLuF4:15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy, Int. J. Miner. Metall. Mater., 31(2024), No. 3, pp. 599-610. https://doi.org/10.1007/s12613-023-2717-3

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Research Article

Establishment of NaLuF₄:15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

+ Author Affiliations

1)
Department of Radiation Oncology, Xijing Hospital, The Fourth Military Medical University, Xi’an 710032, China
2)
Department of Oncology, Air Force Medical Center, PLA, The Fourth Military Medical University, Beijing 100142, China
3)
Department of Tumor Radiotherapy, Air Force Medical Center, PLA, The Fourth Military Medical University, Beijing 100142, China
4)
Department of Gastroenterology, Air Force Hospital of Southern Theater Command, Guangzhou 510062, China
5)
Department of Pharmaceutical Chemistry and Analysis, School of Pharmacy, The Fourth Military Medical University, Xi’an 710032, China
6)
School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China
7)
Institue of Materia Medica, School of Pharmacy, The Fourth Military Medical University, Xi’an 710032, China

Corresponding authors:
Qian Yang    E-mail: 12154521@qq.com

Yu Wang    E-mail: wangyufmmu@163.com

Mei Shi    E-mail: mshi82@fmmu.edu.cn
Received: 9 June 2023; Revised: 20 July 2023; Accepted: 7 August 2023; Available online: 10 August 2023

Abstract

Abstract

X-ray excited photodynamic therapy (X-PDT) is the bravo answer of photodynamic therapy (PDT) for deep-seated tumors, as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth. However, high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application. To address this issue, this work employed a classical co-precipitation reaction to synthesize NaLuF₄:15%Tb³⁺ (NLF) with an average particle size of (23.48 ± 0.91) nm, which was then coupled with the photosensitizer merocyanine 540 (MC540) to form the X-PDT system NLF–MC540 with high production of singlet oxygen. The system could induce antitumor efficacy to about 24% in relative low dose X-ray irradiation range (0.1–0.3 Gy). In vivo, when NLF–MC540 irradiated by 0.1 Gy X-ray, the tumor inhibition percentage reached 89.5% ± 5.7%. The therapeutic mechanism of low dose X-PDT was found. A significant increase of neutrophils in serum was found on the third day after X-PDT. By immunohistochemical staining of tumor sections, the Ly6G⁺, CD8⁺, and CD11c⁺ cells infiltrated in the tumor microenvironment were studied. Utilizing the bilateral tumor model, the NLF–MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth. Detected by enzyme linked immunosorbent assay (ELISA), two cytokines IFN-γ and TNF-α in serum were upregulated 7 and 6 times than negative control, respectively. Detected by enzyme linked immune spot assay (ELISPOT), the number of immune cells attributable to the IFN-γ and TNF-α levels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group, respectively. Thus, it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells, stimulate the secretion of cytokines (especially IFN-γ and TNF-α), activate antitumor immunity, and finally inhibit colon tumor growth.
- X-ray excited photodynamic therapy;
- singlet oxygen;
- low dose X-Ray irradiation;
- efficient antitumor therapy;
- anti-tumor immunity

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