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基于量子点的分子信标用于体外和体内检测肿瘤中的 MMP-2。

Quantum dots based molecular beacons for in vitro and in vivo detection of MMP-2 on tumor.

机构信息

Department of Biomedical Engineering, China Pharmaceutical University, Nanjing 210009, China; School of Pharmacy, Xinjiang Medical University, Urumqi, Xinjiang 830011, China.

Department of Biomedical Engineering, China Pharmaceutical University, Nanjing 210009, China.

出版信息

Biosens Bioelectron. 2014 Nov 15;61:512-8. doi: 10.1016/j.bios.2014.05.035. Epub 2014 Jun 4.

Abstract

Matrix metalloproteinase-2 (MMP-2) is a protease related to tumor invasion and metastasis. It is heavily secreted by malignant tumor cells, allowing the protease to serve as an imaging biomarker of cancer. In this study, a novel sensing system based on fluorescence resonance energy transfer (FRET) from quantum dot (QD, the donor) to organic dye (the acceptor) was constructed for the in vitro and in vivo detection of matrix metalloproteinases-2 via a MMP-2-specific peptide substrate (GPLGVRGKGG). Specifically, 535 nm-emitting CdTe QD were bound to Rhodamine B (RB) through the peptide for in vitro detection of MMP-2, while 720 nm-emitting CdTeS QDs was linked to near infrared dye ICG-Der-02 (MPA) by the peptide for measurement in vivo. When these probes were exposed to MMP-2, the selective cleavage of the peptide resulted in the recovery of fluorescence from QDs. By using the produced 540QD-peptide-RB and 720QD-peptide-MPA probes, we successfully examined MMP-2 in live cells and tumor on nude mouse, respectively. Due to the tunable fluorescence of Qds, this nanosensor can be fine-tuned for a wide range of applications such as the detection of different biomarkers and early diagnosis of disease.

摘要

基质金属蛋白酶-2(MMP-2)是一种与肿瘤侵袭和转移有关的蛋白酶。它由恶性肿瘤细胞大量分泌,使蛋白酶成为癌症的成像生物标志物。在这项研究中,构建了一种基于量子点(QD,供体)到有机染料(受体)的荧光共振能量转移(FRET)的新型传感系统,通过 MMP-2 特异性肽底物(GPLGVRGKGG)用于体外和体内检测基质金属蛋白酶-2。具体来说,通过肽将 535nm 发射的 CdTe QD 与 Rhodamine B(RB)结合,用于 MMP-2 的体外检测,而 720nm 发射的 CdTeS QD 通过肽与近红外染料 ICG-Der-02(MPA)连接,用于体内测量。当这些探针暴露于 MMP-2 时,肽的选择性切割导致 QD 荧光的恢复。通过使用产生的 540QD-肽-RB 和 720QD-肽-MPA 探针,我们成功地分别在活细胞和裸鼠肿瘤中检测了 MMP-2。由于 Qds 的荧光可调谐性,这种纳米传感器可以进行微调,以满足广泛的应用需求,例如检测不同的生物标志物和疾病的早期诊断。

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