Gold Nanoparticle-based Scaffolds for Targeted Imaging and Tissue Ablation
R. Pasqualini, W. Arap
The University of Texas M. D. Anderson Cancer Center, US
Keywords: in vivo phage display, gold nanoparticles, vascular targeting, molecular imaging
Abstract:Blood vessels acquire distinctive molecular signatures in certain diseases. The identification of such markers based on the screening of combinatorial phage peptide libraries offers unique opportunities to achieve high selectivity upon systemic administration of imaging tracers and drugs. We developed novel biotechnology platforms that rely on the spontaneous molecular assembly of gold nanoparticles onto bacteriophage for targeted imaging and selective tissue ablation. The gold nanoassembly (Au-phage scaffold) allows for imaging and ablation properties induced by near-infrared light. As proof-of-concept, have been developing nanotechnology-basesd systems towards targeting of two highly prevalent diseases: atherosclerosis and chronic pulmonary obstructive disease. We have identified molecular receptors by in vivo and ex vivo phage display, selected specific ligands for such receptors by phage display strategies, and evaluated, validated, and prioritized biomarkers of cardiovascular and pulmonary diseases and molecular targets based on ligand-receptor systems. Directed assembly of gold nanoparticles (implantable and injectable) for disease surveillance and targeted delivery, combined with suitable hardware and imaging systems for the detection of nanoparticles in vivo and ex vivo have been studied. Nanodevices for targeted imaging and tissue ablation in the context of cardiovascular and lung disorders are being optimized. Earlier detection and targeted ablation of atheroma plaques has potential to modify the course of atherosclerosis; targeted ablation of pulmonary circulation can elucidate critical molecular and cellular elements involved in emphysema and lung structural maintenance. Furthermore, targeted imaging of the lung vasculature may improve the diagnosis in patients with diseases of the respiratory system. Our overall strategy relies on applying nanotechnology platforms that will allow the molecular interrogation of biologically relevant processes. Subsequently, our observations may lead to a large scale validation using archived material and biological samples from large numbers of patient-derived specimens.