Abstract 4344: Virus-templated magnetic nanowires for tumor-targeted imaging

Abstract

Abstract In an effort towards early tumor detection, various diagnostic probes, such as tumor marker-specific fluorescent and magnetic nanoparticles, have been developed. Nanoparticles detected using magnetic resonance (MR) imaging is an attractive approach due to its non-invasiveness. Current work has focused on single functionalized spherical nanoparticle systems, one example being cross-linked iron oxide nanoparticles (CLIO). However, these ‘shaped’ particles can be cleared by the reticuloendothelial system upon intravenous injection due to opsonization. Recent work suggests that longer filamentous shaped structures can persist almost 10 times longer in circulation in vivo compared to spherical particles. For clinical diagnostics, it would be desirable to engineer filamentous shaped imaging agents that allow for longer circulation and better homing towards the tumor before immune clearance. M13 filamentous bacteriophage can potentially allow for longer circulation of the imaging agents. Recent work indicates that the virus can circulate in vivo for at least 24 hours compared to the 5-6 hour circulation of various spherical particles (unpublished data). Using the M13 virus as a scaffold, we can uniquely combine multiple nanoparticles with engineered cell-targeting peptide ligands for tumor-targeted imaging. Exploiting the multiple coat proteins on M13 amenable for peptide display, we have genetically engineered peptides that bind iron oxide nanoparticles (γ-Fe2O3 NPs) and that target secreted protein, acidic and rich in cysteine (SPARC), a protein overexpressed in metastatic prostate and breast cancers. We have been able to assemble monocrystalline, monodisperse γ-Fe2O3 NPs along the virus coat and demonstrate enhanced MR contrast properties, compared to commercially available CLIO. We have investigated specific targeting against prostate cancer in vitro and in vivo. There is a decrease in transverse relaxation times (‘dark contrast’) using targeted nanowires compared to negative control and is specific towards SPARC positive C4-2B cell line compared to DU145 control. SPARC-targeted nanowires were injected intravenously in LNCaP and C4-2B and control DU145 xenograft tumors. MR images indicate dark image contrast in SPARC expressing tumors, compared to control. Histology suggests iron accumulation in the stroma and capsule of SPARC-positive tumors compared to control, suggesting tumor targeting in vivo. These virus-templated probes may have potential as long circulating, targeted non-invasive imaging agents for the early detection of tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4344.