简介：光热疗法（PTT）在治疗恶性肿瘤方面具有巨大潜力。然而，传统的单一PTT往往难以有效抑制肿瘤转移和复发。在这项研究中，我们构建了一种具有光热和免疫治疗协同治疗作用的MOF纳米颗粒，能够选择性阻断肿瘤微环境中的PD-1/PD-L1通路。方法：首先以NH2-TPDC为配体，Zr 4 为金属离子合成MOF纳米颗粒。随后，通过叠氮化物转移试剂将 NH2 修饰为 N3。通过无铜催化点击化学反应，将DBCO二硫键功能化的PD-1/PD-L1阻断剂AUNP-12共价引入到MOF纳米粒子上，然后负载光热剂吲哚菁绿（ICG），成功获得尺寸均匀且稳定的 ICG-MOF-SS-AUNP12 纳米颗粒。结果和讨论：ICG-MOF-SS-AUNP12 表现出 GSH 触发的 PD-1/PD-L1 阻断剂释放，同时表现出能够有效杀死肿瘤细胞的有效光热效应。在808 nm近红外（NIR）照射下，ICG-MOF-SS-AUNP12有效促进DC细胞成熟并激活免疫反应。该研究提出了一种构建基于MOF的纳米药物的新方法，为光热联合免疫疗法协同治疗肿瘤提供了新的可能性。版权所有©2023Hao、Liu、Zhou、Peng、Li和Chen。

Introduction: Photothermal therapy (PTT) holds significant potential for the treatment of malignant tumors. However, conventional single PTT often struggles to effectively inhibit tumor metastasis and recurrence. In this study, we constructed a MOF nanoparticle with a synergistic therapeutic effect combining photothermal and immunotherapy, enabling selective blocking of the PD-1/PD-L1 pathway within the tumor microenvironment. Methods: Firstly, MOF nanoparticles were synthesized using NH2-TPDC as ligands and Zr+4 as metal ions. Subsequently, NH2 was modified to N3 via azide transfer reagents. Through a copper free catalytic click chemical reaction, the PD-1/PD-L1 blocking agent AUNP-12 functionalized with disulfide bonds of DBCO was covalently introduced into MOF nanoparticles which were then loaded with the photothermal agent indocyanine green (ICG) to successfully obtain uniformly sized and stable ICG-MOF-SS-AUNP12 nanoparticles. Results and discussion: ICG-MOF-SS-AUNP12 exhibited GSH-triggered release of PD-1/PD-L1 blockers while demonstrating potent photothermal effects capable of efficiently killing tumor cells. Under 808 nm near-infrared (NIR) irradiation, ICG-MOF-SS-AUNP12 effectively promoted the maturation of DC cells and activated immune responses. This study presents a novel method for constructing MOF-based nanodrugs and offers new possibilities for the synergistic treatment of tumors involving photothermal combined with immunotherapy.Copyright © 2023 Hao, Liu, Zhou, Peng, Li and Chen.