Multifunctional hybrid iron oxide gold nanoparticles functionalized with MMP enzyme responsive peptides for MRI applications

Multifunctional nanostructured systems have emerged as powerful tools in biomedical applications, including drug delivery, magnetic hyperthermia, molecular imaging, and theranostics. Among these, MRI guided approaches are particularly attractive due to their no invasive nature and high spatial resolution, enabling the development of targeted diagnostic and therapeutic strategies. In this context, we synthesized hybrid iron oxide gold nanoparticles (IONPs-Au) and subsequently functionalized them with a Cy5 labeled peptide containing the Matrix metalloproteinases MMP-2 and MMP-9 cleavable sequence PLGLA. MMP-2 and MMP-9 play a critical role in cancer progression by degrading components of the extracellular matrix, thereby facilitating tumor invasion, metastasis, and angiogenesis. This system enables dual function by combining the potential of magnetic resonance imaging (MRI) with enzyme activated fluorescence. Upon enzymatic cleavage by MMP-2 or MMP-9, the Cy5 fluorophore is released, producing a fluorescence signal that reflects both enzymatic activity and nanoparticle localization. The nanoparticles were characterized using UV–Vis spectrophotometry, FT-IR spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering (DLS). The IONPs-Au exhibited a predominantly spherical morphology with a metal core size generally below 100 nm, providing good MRI contrast at nanoparticle concentrations below 10 mg/mL. Cy5 release was detected via fluorescence microscopy by testing the nanoparticles in 4T1, RAW, and 3T3 cell lines, without inducing cellular toxicity in any case. These results support the potential of this biocompatible IONPs-Au-peptide platform for future MRI-based diagnostic applications targeted to MMP-2 and MMP-9 rich tumor and inflammatory microenvironments.