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原位自组装纳米纤维精准靶向癌相关成纤维细胞以改善肿瘤成像。

In Situ Self-Assembled Nanofibers Precisely Target Cancer-Associated Fibroblasts for Improved Tumor Imaging.

机构信息

CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, 100190, China.

Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China.

出版信息

Angew Chem Int Ed Engl. 2019 Oct 21;58(43):15287-15294. doi: 10.1002/anie.201908185. Epub 2019 Sep 12.

Abstract

Tumor complexity makes the development of highly sensitive tumor imaging probes an arduous task. Here, we construct a peptide-based near-infrared probe that is responsive to fibroblast activation protein-α (FAP-α), and specifically forms nanofibers on the surface of cancer-associated fibroblasts (CAFs) in situ. The assembly/aggregation-induced retention (AIR) effect results in enhanced accumulation and retention of the probe around the tumor, resulting in a 5.5-fold signal enhancement in the tumor 48 h after administration compared to that of a control molecule that does not aggregate. The probe provides a prolonged detectable window of 48 h for tumor diagnosis. The selective assembly of the probe results in a signal intensity over four- and fivefold higher in tumor than in the liver and kidney, respectively. With enhanced tumor imaging capability, this probe can visualize small tumors around 2 mm in diameter.

摘要

肿瘤的复杂性使得开发高灵敏度的肿瘤成像探针成为一项艰巨的任务。在这里,我们构建了一种基于肽的近红外探针,该探针对成纤维细胞激活蛋白-α(FAP-α)有响应,并在原位特异性地在癌相关成纤维细胞(CAFs)表面形成纳米纤维。组装/聚集诱导保留(AIR)效应导致探针在肿瘤周围的积累和保留增强,与不聚集的对照分子相比,给药后 48 小时肿瘤的信号增强了 5.5 倍。该探针为肿瘤诊断提供了长达 48 小时的可检测窗口。探针的选择性组装导致肿瘤的信号强度比肝脏和肾脏分别高出 4 倍和 5 倍。这种探针具有增强的肿瘤成像能力,可以可视化直径约为 2 毫米的小肿瘤。

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