Acute pulmonary infections, acute lung injury, acute vascular injury and atherosclerosis are four of the most prevalent conditions, of immediate NHLBI relevance, that do not have adequate diagnostic or treatment protocols and could benefit significantly from nanotechnological medical devices for noninvasive imaging and selective therapeutic delivery. This PEN integrates a team of multi-disciplinary investigators who will develop unique nanoscale devices to target, image and treat each of these unmet medical needs. Four Projects and two Developmental Projects will be supported by three Cores to develop degradable, organic polymer-based nanomaterials with controlled size, shape, composition and surface chemistry to achieve appropriate biodistribution and targeting to the sites of disease, controlled surface ligand distribution to optimize molecular recognition of the specific biomarkers for each disease, and controlled release of payload to provide therapeutic benefits. Our team brings together select experts in each of the scientific and clinical disciplines that will be required to advance unique nanotechnologies for their translation to clinical application. We also draw upon cutting-edge laboratory tools, from synthetic chemistry and materials science to nanoscale characterization facilities to state-of-the-art imaging systems, and world-class medical facilities. We span three states and five institutions (Washington University, Texas A&M University, University of California, Berkeley, University of California, Santa Barbara, University of Texas Southwest Medical Branch), with a demonstrated ability to sustain highly productive collaborations among our members, to provide far-reaching impact on the research and educational programs across the U.S.