Protease-specific nanosensors for magnetic resonance imaging

Area of Science:

• Molecular Imaging
• Nanotechnology
• Biomedical Engineering

Background:

• Enzyme activity imaging is crucial for molecular imaging research.
• Optical imaging with fluorescent probes is common for in vivo enzyme activity detection.
• A need exists for non-optical modalities like magnetic resonance imaging (MRI) for enzyme activity visualization.

Purpose of the Study:

• To develop a novel high-relaxivity nanosensor for in vivo protease activity imaging using MRI.
• To demonstrate the principle using matrix metalloproteinase 9 (MMP-9), a key enzyme in various diseases.

Main Methods:

• Designed protease-specific iron oxide particles (PSOP) based on clinically tested very small iron oxide particles (VSOP).
• Engineered PSOP to switch from a low-relaxivity stealth state to an adhesive, high-relaxivity state upon MMP-9 cleavage.
• Utilized a specific cleavage motif for matrix metalloproteinase 9 (MMP-9).

Main Results:

• Developed 25 nm hydrodynamic diameter PSOP that are activatable in vivo.
• Demonstrated rapid activation of PSOP upon protease cleavage, leading to particle aggregation.
• Observed a significant increase in T2*-relaxivity post-activation, indicating enhanced MRI contrast.

Conclusions:

• The novel PSOP serve as an effective nanosensor for in vivo magnetic resonance imaging of protease activity.
• This technology holds potential for imaging diseases associated with MMP-9, such as inflammation and cancer.
• The switchable relaxivity mechanism offers a promising approach for molecular MRI.