(405a) Inflamed Leukocyte-Mimetic Nanoparticles for Molecular Imaging of Inflammation: Application to Detection of Tumor and Acute Inflammation

摘要

This study presents physiology-inspired design of superparamagnetic iron oxide (SPIO) nanoparticles for in vivo detection by optical imaging and MRI, mimicking activated leukocyte in its ability to recognize inflamed endothelium. Nanoparticles in vivo will experience hydrodynamic force induced by the blood flow, requiring simultaneous molecular interactions with sufficient adhesion strength with the cells for nanoparticles to remain on the cell surface. Therefore, the design of nanoparticles with tunable affinity and avidity of physiological interactions would be critical to the selectivity and efficiency of targeting. Here we demonstrate specific accumulation of systemically-delivered nanoparticles mimicking the behavior of inflamed leukocytes into tumor cells overexpressing ICAM-1" and the surrounding vascular microenvironment. Further findings of our leukocyte-mimetic nanoparticles (LMN) localizing to the inflamed vasculature of tumors expressing low level of ICAM-1 highlight a potential use of LMN for detection of tumor growth by their accumulation into the inflammatory tumor microenvironment, irrespective of the type of tumor surface antigen.