Accurate targeting of activated macrophages based on synergistic activation of functional molecules uptake by scavenger receptor and matrix metalloproteinase.
Specific targeting of disease cells has the potential of far-reaching applications, such as diagnostic imaging and therapies of diseases. Here we describe a novel method for selective targeting of a type of cells among various cell types. Activated macrophages are disease cells related to initiation and progression of atherosclerosis. We developed a molecular probe of which uptake into cells is synergistically activated by scavenger receptor class A type I (SR-AI) and matrix metalloproteinase-9 (MMP-9), which are the marker receptor and the marker protease of atherosclerosis, respectively. We demonstrated that the present targeting probe is selectively incorporated into activated macrophages expressing both SR-AI and the activated form of MMP-9 but not into resting macrophages having only SR-AI. The present approach may provide a powerful tool for cell-specific imaging and therapies.
Suzuki
Hideyuki
H
Sato
Moritoshi
M
Umezawa
Yoshio
Y
D000818:Animals; D001055:Apolipoproteins B / Q000737:chemistry / Q000494:pharmacology; D050197:Atherosclerosis / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004357:Drug Synergism; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D015335:Molecular Probes / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology; D051117:Scavenger Receptors, Class A / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D001055:Apolipoproteins B; D015335:Molecular Probes; D011993:Recombinant Fusion Proteins; D051117:Scavenger Receptors, Class A; D049452:Green Fluorescent Proteins; D020780:Matrix Metalloproteinase 9