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納米粒度測量應用案例-58-Omni

閱讀:154          發布時間:2015-7-23
 文獻名: Delivery of Lipid Micelles into Infarcted 
 
Myocardium Using a Lipid-Linked Matrix Metalloproteinase 
 
Targeting Peptide
 
作者: Juliane Nguyen *†, Richard Sievers ‡, J. P. Michael 
 
Motion §, Saul Kivimäe §, Qizhi Fang ‡, and Randall J. 
 
Lee *‡
† Department of Pharmaceutical Sciences, School of Pharmacy 
 
and Pharmaceutical Sciences, University at Buffalo, The 
 
State University of New York, Buffalo, New York 14214, 
 
United States
‡ Department of Medicine, Cardiovascular Research 
 
Institute, and Institute of Regeneration Medicine, 
 
University of California—San Francisco, San Francisco, 
 
California 94143, United States
§ Department of Bioengineering and Therapeutic Sciences, 
 
University of California—San Francisco, San Francisco, 
 
California 94143, United States
 
摘要:There is a great need for delivery strategies capable 
 
of efficiently localizing drugs to the damaged myocardium 
 
that do not require direct intramyocardial injection of 
 
therapeutic molecules. In the work discussed here, we 
 
exploited the myocardium-specific upregulation of matrix 
 
metalloproteinases (MMPs) that occurs during myocardium 
 
remodeling by designing a micellar vehicle containing an 
 
MMP-targeting peptide (MMP-TP). The binding of MMP-TP to 
 
MMP was evaluated with purified MMP-2 protein and U-937 
 
cells induced to overexpress MMP. Inhibition of MMP-2 
 
activity was not observed in the presence of unmodified 
 
micelles but was pronounced at a 5 mol % MMP-TP ligand 
 
density. In a FACS analysis, MMP-TP micelles containing 5 
 
mol % of the MMP-targeting peptide showed ∼10-fold higher 
 
binding to activated U937 cells than plain micelles and 
 
micelles containing a control peptide with two amino acid 
 
replacements. MMP-TP-micelles and plain micelles were 
 
injected intravenously into C57BL/6 mice 1, 3, and 7 days 
 
after the induction of a myocardial infarction (MI). 
 
Immunohistochemistry performed on heart tissue sections 
 
revealed that MMP-TP-micelles colocalize with both MMP and 
 
infiltrating macrophages. MMP-TP micelles showed 
 
significantly enhanced accumulation to the necrotic area of 
 
the heart after MI on days 3 and 7 when compared to plain 
 
micelles and negative control peptide micelles. This is 
 
coincident with the measured temporal profile of MMP gene 
 
expression in the heart after MI. These results suggest 
 
that MMP-TP micelles are candidates for the development of 
 
targeted regenerative heart therapeutics because of their 
 
ability to target the infarcted myocardium in a MMP 
 
dependent manner.
 
關鍵詞:myocardial infarction; matrix metalloproteinase; 
 
targeted micellar vehicles; drug targeting

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