A ratiometric fluorescent probe based on peptide modified MnFe 2 O 4 nanoparticles for matrix metalloproteinase-7 activity detection in vitro and in vivo .

Abnormal expression of matrix metalloproteinases plays an important role in tumor invasion and metastasis. In this report, a peptide modified MnFe 2 O 4 ratiometric fluorescent nanoprobe is developed for noninvasively visualizing the distribution of matrix metalloproteinase-7 (MMP-7) in vitro and in vivo . A fluorescein isothiocyanate (FITC) modified peptide containing the specific motif VPLSLTMG for MMP-7 cleavage was conjugated with MnFe 2 O 4 nanoparticles (NPs) to establish a Förster resonance energy transfer (FRET) system for sensing the protease. The rhodamine B (RhB) modified targeting peptide immobilized on the nanoparticle surface was not only used as an internal reference for forming a ratiometric fluorescence system together with the FITC dye, but also used for enhancing the tumor targeting ability. The tumor accumulation amount of the as-developed ratiometric fluorescent probe (termed MnFe 2 O 4 -pep-dyes) can be measured by T 2 -weighted magnetic resonance ( T 2 -weighted MR) imaging because MnFe 2 O 4 NPs display an excellent T 2 -weighted MR contrast ability. In the presence of MMP-7, FITC detached from the MnFe 2 O 4 surface resulting in the recovery of FITC fluorescence, while no obvious change of the RhB fluorescence was observed. The recovery ratio of FITC to RhB fluorescence intensity is linearly dependent on the MMP-7 concentration within the range of 0.1 to 15 nM in buffer and 5 × 10 2 to 1 × 10 4 cells in cell lysates with a limit of detection of 0.1 nM and 436 cells, respectively. MnFe 2 O 4 -pep-dyes was further applied to spatially observe MMP-7 expression in a tumor-bearing mouse by in vivo fluorescence imaging with external magnetic field assistance for demonstrating its practicability.