Targeted delivery of MMP14 inhibitor in a nanodrug construct for stabilization of unstable atherosclerotic plaques to prevent plaque rupture

The purpose of this research is to design a targeted nanoparticle drug construct with the ability to penetrate the unstable atherosclerotic plaque, stabilize it; as a form of therapy for translation into a prophylaxis against human heart attacks The fully assembled drug construct is a modular prototype of a targeted delivery platform and it comprises 3 components - collagen IV binding heptapeptide, the activatable cell penetrating peptide designed for MMP2 cleavage and the nanosponge loaded with the MMP14 inhibitor drug, Naphthofluoroscein.The research could demonstrate specific entry and lodgment of the fully assembled construct in unstable mouse plaques. Therapy with 2 doses of this construct spread over 4 weeks was found to significantly reduce the MMP14 activity, significantly increase the collagen content of the plaques and mildly reduce the presence of platelets in the treated unstable plaques using the tandem stenosis mouse model of plaque instability.