Zoledronic Acid-Gadolinium Coordination Polymer Nanorods for Improved Tumor Radioimmunotherapy by Synergetically Inducing Immunogenic Cell Death and Reprogramming the Immunosuppressive Microenvironment

被引:70
|
作者
Huang, Zhusheng [1 ]
Yao, Dan [1 ]
Ye, Qingsong [1 ]
Jiang, Haojie [1 ]
Gu, Rong [1 ]
Ji, Changwei [3 ]
Wu, Jinhui [1 ,2 ]
Hu, Yiqiao [1 ,2 ]
Yuan, Ahu [1 ,2 ]
机构
[1] Nanjing Univ, Med Sch & Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China
[2] Nanjing Univ, Jiangsu Key Lab Nano Technol, Nanjing 210093, Peoples R China
[3] Nanjing Univ, Affiliated Nanjing Drum Tower Hosp, Urol Dept, Nanjing 210093, Peoples R China
关键词
carrier-free; coordination polymer nanorods; radioimmunotherapy; immunogenic cell death; tumor immunosuppressive microenvironment; tumor-associated macrophages; RADIATION-THERAPY; RADIOTHERAPY; CANCER; TOXICITY; NANOPARTICLES; BISPHOSPHONATES; MACROPHAGES; IMMUNOLOGY; RESISTANCE;
D O I
10.1021/acsnano.0c10764
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Radiation therapy can potentially elicit a systemic immune response and cause the regression of nonirradiated tumors, and the checkpoint blockade immunotherapies have been introduced to improve their clinical response rate. However, the therapeutic benefits of radioimmunotherapy are still far from satisfactory. Herein, the self-assembled "carrier-free" coordination polymer nanorods are constructed based on gadolinium and zoledronic acid, which can deposit X-ray for improved reactive oxygen species production to induce potent immunogenic cell death (ICD), simultaneously deplete tumor-associated macrophages with regulatory cytokines inhibition, respectively. With the potent ICD induction and reprogrammed immunosuppressive microenvironment, this synergetic strategy can promote antigen presentation, immune priming and T-cell infiltration, and potentiate checkpoint blockade immunotherapies against primary, distant, and metastatic tumors.
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页码:8450 / 8465
页数:16
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