Abiotic Mimic of Matrix Metalloproteinase-9 Inhibitor against Advanced Metastatic Cancer

Area of Science:

• Biomaterials Engineering
• Nanotechnology
• Cancer Biology

Background:

• Matrix metalloproteinase-9 (MMP-9) is crucial in tumorigenesis, promoting cancer cell migration and tumor microenvironment regulation.
• Targeting MMP-9 is a therapeutic strategy, but synthetic inhibitors lack selectivity, leading to clinical trial failures.

Purpose of the Study:

• To design and synthesize an abiotic mimic for selective MMP-9 inhibition.
• To develop molecularly imprinted nanoparticles as a novel anticancer therapeutic agent.

Main Methods:

• Synthesized imprinted polymer thin layers on gold nanorods using MMP-9 as a template via reversible addition-fragmentation chain transfer polymerization.
• Evaluated selective MMP-9 capture and activity inhibition through steric hindrance.
• Conducted in vitro cell experiments and in vivo studies in mice.

Main Results:

• The MMP-9-imprinted nanoparticles selectively captured and inhibited MMP-9 activity.
• Demonstrated suppression of metastatic tumor migration and growth in mice, with a tumor growth inhibition rate of up to 54 ± 15%.
• Showed superior inhibition of lung tumor metastasis compared to photothermal therapy alone by quenching MMP-9 activity.

Conclusions:

• Engineered MMP-9-imprinted nanoparticles serve as effective abiotic mimics for selective enzyme inhibition.
• This approach offers a new paradigm for developing nanoparticle-based inhibitors for cancer therapy.
• The study highlights the potential of imprinted nanoparticles in suppressing tumor metastasis.