Tantalum-Zirconium Co-Doped Metal-Organic Frameworks Sequentially Sensitize Radio-Radiodynamic-Immunotherapy for Metastatic Osteosarcoma

作者全名："Li, Tao; Gao, Mingquan; Wu, Zifei; Yang, Junjun; Mo, Banghui; Yu, Songtao; Gong, Xiaoyuan; Liu, Jing; Wang, Weidong; Luo, Shenglin; Li, Rong"

作者地址："[Li, Tao; Gao, Mingquan; Wu, Zifei; Liu, Jing; Luo, Shenglin; Li, Rong] Third Mil Med Univ, Army Med Univ, Chongqing Engn Res Ctr Nanomed, State Key Lab Trauma Burns & Combined Injury,Coll, Chongqing 400038, Peoples R China; [Li, Tao; Yang, Junjun; Gong, Xiaoyuan] Third Mil Med Univ, Army Med Univ, Southwest Hosp, Ctr Joint Surg, Chongqing 400038, Peoples R China; [Gao, Mingquan; Wu, Zifei; Wang, Weidong] Sichuan Canc Hosp & Inst, Dept Radiat Oncol, Sichuan Key Lab Radiat Oncol, Chengdu 610041, Sichuan, Peoples R China; [Mo, Banghui; Yu, Songtao] Third Mil Med Univ, Army Med Univ, Southwest Hosp, Dept Oncol, Chongqing 400038, Peoples R China"

通信作者："Luo, SL; Li, R (通讯作者)，Third Mil Med Univ, Army Med Univ, Chongqing Engn Res Ctr Nanomed, State Key Lab Trauma Burns & Combined Injury,Coll, Chongqing 400038, Peoples R China.; Wang, WD (通讯作者)，Sichuan Canc Hosp & Inst, Dept Radiat Oncol, Sichuan Key Lab Radiat Oncol, Chengdu 610041, Sichuan, Peoples R China."

来源：ADVANCED SCIENCE

ESI学科分类：PHYSICS

WOS号：WOS:000965739800047

JCR分区：Q1

影响因子：15.1

年份：2023

卷号：10

期号：10

开始页：　

结束页：　

文献类型：Article

关键词：cancer theranostics; immunotherapy; metal-organic frameworks; radiodynamic therapy; radiosensitizers

摘要："Due to radiation resistance and the immunosuppressive microenvironment of metastatic osteosarcoma, novel radiosensitizers that can sensitize radiotherapy (RT) and antitumor immunity synchronously urgently needed. Here, the authors developed a nanoscale metal-organic framework (MOF, named TZM) by co-doping high-atomic elements Ta and Zr as metal nodes and porphyrinic molecules (tetrakis(4-carboxyphenyl)porphyrin (TCPP)) as a photosensitizing ligand. Given the 3D arrays of ultra-small heavy metals, porous TZM serves as an efficient attenuator absorbing X-ray energy and sensitizing hydroxyl radical generation for RT. Ta-Zr co-doping narrowed the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy gap and exhibited close energy levels between the singlet and triplet photoexcited states, facilitating TZM transfer energy to the photosensitizer TCPP to sensitize singlet oxygen (O-1(2)) generation for radiodynamic therapy (RDT). The sensitized RT-RDT effects of TZM elicit a robust antitumor immune response by inducing immunogenic cell death, promoting dendritic cell maturation, and upregulating programmed cell death protein 1 (PD-L1) expression via the cGAS-STING pathway. Furthermore, a combination of TZM, X-ray, and anti-PD-L1 treatments amplify antitumor immunotherapy and efficiently arrest osteosarcoma growth and metastasis. These results indicate that TZM is a promising radiosensitizer for the synergistic RT and immunotherapy of metastatic osteosarcoma."

基金机构："National Natural Science Foundation of China [82173456, 82173457]; Key Projects of Sichuan Natural Science Foundation [2022NSFSC0051]; Chongqing Natural Science Foundation [cstc2021jcyj-msxmX0633, cstc2021ycjh-bgzxm0123]; Clinical Scientist Program of Sichuan Cancer Hospital [YB2022003]; Chengdu Technology Innovation RD Project [2021YF0501659SN]"

基金资助正文："T.L. and M.G. contributed equally to this work. This work was supported in part by the National Natural Science Foundation of China (82173456 and 82173457), Key Projects of Sichuan Natural Science Foundation (2022NSFSC0051), Chongqing Natural Science Foundation (cstc2021jcyj-msxmX0633 and cstc2021ycjh-bgzxm0123), Clinical Scientist Program of Sichuan Cancer Hospital (YB2022003), and Chengdu Technology Innovation R&D Project (2021YF0501659SN). The authors thank Knorigene Technologies (Chongqing, China) for providing the gene analysis. BALB/c mice (18-22 g) were obtained from the Laboratory Animal Center of the Third Military Medical University (Chongqing, China). All animal experiments were approved by the Ethics Committee of the Third Military Medical University (Accreditation number, AMUWEC20213589, Chongqing, China)."