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

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.

Keywords: FRET; Matrix metalloproteinase-2; Near infrared imaging; Proteolytic activity; Quantum dots.