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首页> 外文期刊>ACS nano >Multimodal Multiplexed Immunoimaging with Nanostars to Detect Multiple Immunomarkers and Monitor Response to Immunotherapies
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Multimodal Multiplexed Immunoimaging with Nanostars to Detect Multiple Immunomarkers and Monitor Response to Immunotherapies

机译：用纳米螺栓多翻来的免疫分析检测多种免疫标志物和监测对免疫疗法的响应

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摘要

The overexpression of immunomarker programmed cell death protein 1 (PD-I) and engagement of PD-1 to its ligand, PD-L1, are involved in the functional impairment of cluster of differentiation 8(+) (CD8(+)) T cells, contributing to cancer progression. However, heterogeneities in PD-LI expression and variabilities in biopsy-based assays render current approaches inaccurate in predicting PD-L1 status. Therefore, PD-LI screening alone is not predictive of patient response to treatment, which motivates us to simultaneously detect multiple immunomarkers engaged in immune modulation. Here, we have developed multimodal probes, immunoactive gold nanostars (IGNs), that accurately detect PD-L1(+) tumor cells and CD8(+) T cells simultaneously in vivo, surpassing the limitations of current immunoimaging techniques. IGNs integrate the whole-body imaging of positron emission tomography with high sensitivity and multiplexing of Raman spectroscopy, enabling the dynamic tracking of both immunomarkers. IGNs also monitor response to immunotherapies in mice treated with combinatorial PD-L1 and CD137 agonists and distinguish responders from those nonresponsive to treatment. Our results showed a multifunctional nanoscale probe with capabilities that cannot be achieved with either modality alone, allowing multiplexed immunologic tumor profiling critical for predicting early response to immunotherapies.
机译：免疫标志物编程的细胞死亡蛋白质1（PD-1）和PD-1的接合映射到其配体PD-L1，参与分化8（+）（CD8（+））T细胞的功能损伤为癌症进展促进癌症进展。然而，基于活组织检查的测定中的PD-Li表达和变性的异质性呈现预测PD-L1状态的电流接近。因此，单独的PD-Li筛选不是预测对治疗的患者的反应，这激励我们同时检测从事从事免疫调节的多个免疫标记物。在这里，我们已经开发了多峰探针，免疫活性金纳略符号（ICM），其在体内同时准确地检测PD-L1（+）肿瘤细胞和CD8（+）T细胞，超过当前免疫瘤技术的局限性。 IGNS将正电子发射断层扫描的全身成像与拉曼光谱的高灵敏度和多路复用集成，使得免疫标志物的动态跟踪。 IGN也监测用组合PD-L1和CD137激动剂治疗的小鼠中的免疫检查的反应，并将响应者与那些无响应的治疗区分开来。我们的结果表明，多功能纳米尺度探针，其能够单独使用任一种形态实现，允许多重免疫肿瘤谱重，以预测对免疫疗法的早期反应。

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