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近红外荧光分子探针用于瘢痕疙瘩的敏感成像。

Near-Infrared Fluorescent Molecular Probe for Sensitive Imaging of Keloid.

机构信息

School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637457, Singapore.

出版信息

Angew Chem Int Ed Engl. 2018 Jan 26;57(5):1256-1260. doi: 10.1002/anie.201710727. Epub 2018 Jan 5.

Abstract

Early detection of skin diseases is imperative for their effective treatment. However, fluorescence molecular probes that allow this are rare. The first activatable near-infrared (NIR) fluorescent molecular probe is reported for sensitive imaging of keloid cells, skin cells from abnormal scar fibrous lesions. As keloid cells have high expression levels of fibroblast activation protein-alpha (FAPα), the probe (FNP1) is designed to have a caged NIR dye and a FAPα-cleavable peptide substrate linked by a self-immolative segment. FNP1 can quickly and specifically turn on its fluorescence at 710 nm by 45-fold in the presence of FAPα, allowing it to effectively recognize keloid cells from normal skin cells. Integration of FNP1 with a simple microneedle-assisted topical application enables sensitive detection of keloid cells in metabolically-active human skin tissue with a theoretical limit of detection down to 20 000 cells.

摘要

早期发现皮肤疾病对于有效治疗至关重要。然而,能够实现这一目标的荧光分子探针却很少。本文首次报道了一种可激活的近红外(NIR)荧光分子探针,可用于敏感地对瘢痕疙瘩细胞(来源于异常瘢痕纤维病变的皮肤细胞)成像。由于成纤维细胞激活蛋白-α(FAPα)在瘢痕疙瘩细胞中高表达,因此设计探针(FNP1)使其包含一个被笼蔽的近红外染料和一个 FAPα 可切割的肽底物,通过自毁片段连接。FNP1 在 FAPα 的存在下,可快速且特异性地将其荧光在 710nm 处打开 45 倍,使其能够有效识别瘢痕疙瘩细胞与正常皮肤细胞。将 FNP1 与简单的微针辅助局部应用相结合,可实现对代谢活跃的人皮肤组织中瘢痕疙瘩细胞的灵敏检测,理论检测下限低至 20000 个细胞。

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