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.