In Vivo Targeting of Inflammation-Associated Myeloid-Related Protein 8/14 Via Gadolinium Immunonanoparticles
In Vivo Targeting of Inflammation-Associated Myeloid-Related Protein 8/14 Via Gadolinium Immunonanoparticles
Objective— Myeloid-related protein (Mrp) 8/14 complex (is a highly expressed extracellularly secreted protein, implicated in atherosclerosis. In this study, we evaluated the feasibility of targeting Mrp in vivo through synthetic immuno-nanoprobes. Methods and Results— Anti-Mrp–14 and nonspecific IgG-conjugated gadolinium nanoprobes (aMrp-) were synthesized and characterized. Pharmacokinetics and vascular targeting via MRI of the formulations were assessed in vivo in high fat-fed apolipoprotein E deficient (ApoE −/− ), ApoE −/− /Mrp14 −/− (double knockout) and chow-fed wild-type (C57BL/6) mice. Bone marrow-derived myeloid progenitor cells were isolated from both ApoE −/− and double knockout mice, differentiated to macrophages, and were treated with LPS, with or without Mrp8, Mrp14, or Mrp8/14; conditioned media was used for in vitro studies. Mrp-activated cells secreted significant amounts of proinflammatory cytokines, which was abolished by pretreatment with aMrp-NP. We show in vitro that aMrp-NP binds endothelial cells previously treated with conditioned media containing Mrp8/14. MRI following intravenous delivery of aMrp-NP revealed prolonged and substantial delineation of plaque in ApoE −/− but not double knockout or wild-type animals. Nonspecific IgG-conjugated gadolinium nanoprobe-injected animals in all groups did not show vessel wall enhancement. Flow-cytometric analysis of aortic digesta revealed that aMrp-NP present in Ly-6G + , CD11b + , CD11c + , and CD31 + cells in ApoE −/− but not in double knockout animals. Conclusion— Targeted imaging with aMrp-NP demonstrates enhancement of plaque with binding to inflammatory cells and reduction in inflammation. This strategy has promise as a theranostic approach for atherosclerosis.
- Harvard University United States
- The Ohio State University United States
- University of Central Florida United States
- MetroHealth United States
- Brigham and Women's Faulkner Hospital United States
Gadolinium DTPA, Immunoconjugates, Anti-Inflammatory Agents, Contrast Media, Distributed systems, Antibodies, Apolipoproteins E, Albumins, Spatial databases, Human Umbilical Vein Endothelial Cells, magnetic resonance imaging, APOPTOTIC CELLS, Animals, Calgranulin B, Humans, OXIDIZED, Calgranulin A, CARDIOVASCULAR EVENTS, Cells, Cultured, Inflammation, Mobile computing, MAC-1, BIOLOGICAL RESPONSE, Hematology, Atherosclerosis, Flow Cytometry, ENDOTHELIAL-CELLS, macrophages, imaging agents, PHOSPHATIDYLSERINE LIPOSOMES, PHOSPHOLIPIDS, Disease Models, Animal, Peripheral Vascular Disease, MACROPHAGE FOAM CELL, Culture Media, Conditioned, SCAVENGER RECEPTOR CD36, Cytokines, Feasibility Studies, atherosclerosis, INTEGRIN, VASCULAR INJURY
Gadolinium DTPA, Immunoconjugates, Anti-Inflammatory Agents, Contrast Media, Distributed systems, Antibodies, Apolipoproteins E, Albumins, Spatial databases, Human Umbilical Vein Endothelial Cells, magnetic resonance imaging, APOPTOTIC CELLS, Animals, Calgranulin B, Humans, OXIDIZED, Calgranulin A, CARDIOVASCULAR EVENTS, Cells, Cultured, Inflammation, Mobile computing, MAC-1, BIOLOGICAL RESPONSE, Hematology, Atherosclerosis, Flow Cytometry, ENDOTHELIAL-CELLS, macrophages, imaging agents, PHOSPHATIDYLSERINE LIPOSOMES, PHOSPHOLIPIDS, Disease Models, Animal, Peripheral Vascular Disease, MACROPHAGE FOAM CELL, Culture Media, Conditioned, SCAVENGER RECEPTOR CD36, Cytokines, Feasibility Studies, atherosclerosis, INTEGRIN, VASCULAR INJURY
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