High Throughput and Noninvasive Exosomal PD-L1 Detection for Accurate Immunotherapy Response Prediction via Tim4-Functionalized Magnetic Core-Shell Metal-Organic Frameworks.
High Throughput and Noninvasive Exosomal PD-L1 Detection for Accurate Immunotherapy Response Prediction via Tim4-Functionalized Magnetic Core-Shell Metal-Organic Frameworks.
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DOI：
10.1021/acs.analchem.3c04117
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发表时间：
2023-11
影响因子：
7.4
通讯作者：
Haiyan Wang;Yanli Liu;Liyuan Zhang;Xinran Li;Guofa Zhao;Zi-Zheng Song;Youchao Jia;Xiaoqiang Qiao
中科院分区：
文献类型：
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作者：
Haiyan Wang;Yanli Liu;Liyuan Zhang;Xinran Li;Guofa Zhao;Zi-Zheng Song;Youchao Jia;Xiaoqiang Qiao
外泌体 PD-L1 越来越被认为是免疫治疗反应的无创且准确的预测标志物。然而，外泌体PD-L1表达的临床监测仍然受到其复杂的生物环境以及缺乏稳健的分离策略的限制。在这里，通过逐层组装轻松构建了 Tim4 功能化的磁性核壳金属有机框架（表示为 Fe3O4@SiO2-ILI-01@Tim4）。由于1,3-双(4-羧丁基)溴化咪唑鎓(ILI)的强亲水性有机配体，磁性Fe3O4@SiO2-ILI-01@Tim4具有非特异性吸附低、外泌体分离快速、简便的优点。 Fe3O4@SiO2-ILI-01@Tim4的捕获效率高达90.3±0.5%，外泌体的回收率高达93.0±6.1%。分离的外泌体纯度比超速离心（UC）方法高7.5倍。通过进一步与免疫荧光检测相结合，实现了高通量、无创的外泌体PD-L1检测，以准确预测免疫治疗反应。所开发的基于 Fe3O4@SiO2-ILI-01@Tim4 的策略的预后准确性达到 85.7%，而临床金标准 PD-L1 联合阳性评分 (CPS) 测试的预后准确性仅为 57.1%。最有趣的是，所开发的方法特别适合那些在 CPS 测试中收到假阴性结果的患者。所提出的 Fe3O4@SiO2-ILI-01@Tim4 是一种高效且稳健的技术，在高通量和非侵入性外泌体 PD-L1 检测方面显示出巨大潜力，可准确预测免疫治疗效果。
Exosomal PD-L1 has been increasingly considered a noninvasive and accurate predictive marker for immunotherapy treatment response. However, the clinical monitoring of exosomal PD-L1 expression is still limited by its complex biological environment as well as the lack of a robust isolation strategy. Here, a Tim4-functionalized magnetic core-shell metal-organic framework (denoted as Fe3O4@SiO2-ILI-01@Tim4) was facilely constructed via layer-by-layer assembly. Owing to the strongly hydrophilic organic ligand of 1,3-bis(4-carboxybutyl)imidazolium bromide (ILI), magnetic Fe3O4@SiO2-ILI-01@Tim4 was endowed with the merits of low nonspecific adsorption and quick, easy, and convenient isolation of exosomes. The capture efficiency of Fe3O4@SiO2-ILI-01@Tim4 reached as high as 90.3 ± 0.5% and the recovery rate for exosomes was up to 93.0 ± 6.1%. The purity of the isolated exosomes was 7.5 times higher than that via the ultracentrifugation (UC) method. By further combination with immunofluorescence assay, high throughput and noninvasive exosomal PD-L1 detection for accurate immunotherapy response prediction was achieved. The prognosis accuracy of the developed Fe3O4@SiO2-ILI-01@Tim4-based strategy reached 85.7%, whereas the prognosis accuracy of the clinical gold standard, the PD-L1 combined positive score (CPS) test, was only 57.1%. Most interestingly, the developed method is especially suitable for those patients receiving false negative results in the CPS test. The proposed Fe3O4@SiO2-ILI-01@Tim4 is a highly efficient and robust technique showing great potential in high throughput and noninvasive exosomal PD-L1 detection for accurately predicting immunotherapy efficacy.