Dysprosium-Modified Tobacco Mosaic Virus Nanoparticles for Ultra-High-Field Magnetic Resonance and Near-Infrared Fluorescence Imaging of Prostate Cancer

The increasing prevalence of ultra-high-field nagnetic resonance imaging (UHFMRI) in biomedical research and clinical settings will improve the resolution and diagnostic accuracy of MRI scans. However, better contrast agents are needed to achieve a satisfactory signal-to-noise ratio. Here, we report the synthesis of a bimodal contrast agent prepared by loading the internal cavity of tobacco mosaic virus (TMV) nanoparticles with a dysprosium (Dy3+) complex and the near infrared fluorescence (NIRF) dye Cy7.5. The external surface of TMV was conjugated with an Asp-Gly-Glu-Ala (DGEA) peptide via a polyethylene glycol linker to target integrin alpha(2),beta(1). The resulting nanoparticle (Dy-Cy7.5-TMV-DGEA) was stable and achieved a high transverse relaxivity in ultra-high-strength magnetic fields (326. and 399 mM(-1)s(-1) at 7 and 9.4 T, respectively). The contrast agent was also biocompatible (low cytotoxicity) and targeted PC-3 prostate cancer cells and tumors in vitro and in vivo as confirmed by bimodal NIRF imaging and T-2-mapping UHFMRI. Our results show that Dy-Cy7.5-TMV-DGEA is suitable for multiscale MRI scanning from the cellular level to the whole body, particularly in the context of UHFMRI applications.