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Establishment of NaLuF_(4):15%Tb-based low dose x-PDT agent and its application on efficient antitumor therapy

International Journal of Minerals,Metallurgy and Materials 2024年第3期31卷 599-610页

作者： Yi Tian Zhiguang Fu xiaosheng Zhu Chunjing Zhan Jinwei Hu Li Fan Chaojun Song Qian Yang Yu Wang Mei Shi Department of Radiation Oncology Xijing HospitalThe Fourth Military Medical UniversityXi’an 710032China Department of Oncology Air Force Medical CenterPLAThe Fourth Military Medical UniversityBeijing 100142China Department of Tumor Radiotherapy Air Force Medical CenterPLAThe Fourth Military Medical UniversityBeijing 100142China Department of Gastroenterology Air Force Hospital of Southern Theater CommandGuangzhou 510062China Department of Pharmaceutical Chemistry and Analysis School of PharmacyThe Fourth Military Medical UniversityXi’an 710032China School of Life Sciences Northwestern Polytechnical UniversityXi’an 710072China Institue of Materia Medica School of PharmacyThe Fourth Military Medical UniversityXi’an 710032China

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 ***,high x-ray irradiation dose caused organ lesions and side effects became the major barrier to x-PDT *** address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(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 *** 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 *** immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were *** the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy x-ray irradiation could inhibit both the primary tumor and the distant tumor ***-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,*** by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose x-PDT were 14 and 6 times greater than that in the negative control group,***,it conclude that low dose x-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

关键词： x-ray excited photodynamic therapy singlet oxygen low dose x-ray irradiation efficient antitumor therapy anti-tumor immunity

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