Enzyme-Responsive Nanoparticles for the Targeted Delivery of an MMP Inhibitor to the Heart post Myocardial Infarction
Enzyme-Responsive Nanoparticles for the Targeted Delivery of an MMP Inhibitor to the Heart post Myocardial Infarction
Abstract In this paper, we describe block copolymer amphiphiles consisting of a hydrophilic matrix metalloproteinase (MMP) peptide substrate, and a hydrophobic small molecule MMP inhibitor PD166793 for the treatment of acute myocardial infarction. These resulting drug loaded peptide-polymer amphiphiles (PPAs) assemble in aqueous solution to yield drug loaded micellar nanoparticles. Following minimally invasive intravenous injection, these nanoparticles preferentially exit the vasculature and are physically trapped at the infarcted region of the heart due to MMP-induced peptide cleavage and aggregation. This MMP directed active assembly prevents the material from leaking out into the blood stream, enabling long-term retention. Further, we show that the conjugated MMP inhibitor (PD166793) is inactivated in the core of the micelles and can be released upon the action of proteases and esterases, leading to MMP inhibition. This work establishes a promising targeted nanoparticle platform for delivering small molecule therapeutics to the heart.
Sullivan Holly L.、Luo Colin、Christman Karen L.、Liang Yifei、Worthington Kendra、Gianneschi Nathan C.
Department of Bioengineering and the Sanford Consortium for Regenerative, Medicine, University of CaliforniaDepartment of Bioengineering and the Sanford Consortium for Regenerative, Medicine, University of CaliforniaDepartment of Bioengineering and the Sanford Consortium for Regenerative, Medicine, University of CaliforniaDepartment of Chemistry, International Institute for Nanotechnology, Simpson-Querrey Institute, Chemistry of Life Processes Institute, Northwestern UniversityDepartment of Bioengineering and the Sanford Consortium for Regenerative, Medicine, University of CaliforniaDepartment of Chemistry, International Institute for Nanotechnology, Simpson-Querrey Institute, Chemistry of Life Processes Institute, Northwestern University||Departments of Materials Science & Engineering, Biomedical Engineering and Pharmacology, Northwestern University
医药卫生理论医学研究方法药学生物科学研究方法、生物科学研究技术生物化学生物工程学
Stimuli-responsive polymersring-opening metathesis polymerizationcontrolled releasedrug deliverymyocardial infarction
Sullivan Holly L.,Luo Colin,Christman Karen L.,Liang Yifei,Worthington Kendra,Gianneschi Nathan C..Enzyme-Responsive Nanoparticles for the Targeted Delivery of an MMP Inhibitor to the Heart post Myocardial Infarction[EB/OL].(2025-03-28)[2025-05-16].https://www.biorxiv.org/content/10.1101/2022.03.07.483374.点此复制
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