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

Abstract

The increasing prevalence of ultra-high-field magnetic 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 α2β1. 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 T2-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.

Supramolecular and biomacromolecular enhancement of metal-free magnetic resonance imaging contrast agents

“…24,25 However, two major issues prevent aminoxyl-based ORCAs from replacing traditional contrast agents based on Gd: (i) their single unpaired electron provides weaker contrast compared to the seven unpaired electrons of Gd and (ii) they are reduced rapidly to MRI-silent hydroxylamines in physiological conditions by compounds including ascorbate, saccharides, and cysteine-rich proteins. 24 Contrast issues in ORCAs have improved greatly in recent years by attaching them to polymeric or biomacromolecular nanoparticle systems [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] that both create high local concentrations of aminoxyl moieties and decrease the diffusional and rotational motion of the attached ORCAs. Because rotational correlation time is inversely proportional to relaxivity, attaching contrast agents onto large macromolecules will-in generalimprove their performance.…”

Interactions Between Tumor Biology and Targeted Nanoplatforms for Imaging Applications

“…The robust molecular structure of tobacco mosaic virus (TMV) offers a versatile platform for theranostic applications. The Hu group184 synthesized a bimodal imaging agent by loading the internal cavity of TMV self‐assembled NPs with a NIRF dye Cy7.5 dysprosium ions (Dy 3+ ) to produce a complex. The imaging probe was then conjugated with Asp‐Gly‐Glu‐Ala (DGEA) peptide that targets integrin α2β1.…”

Speciation of Phenanthriplatin and Its Analogs in the Core of Tobacco Mosaic Virus

“…42–45 The inner lining of the channel is highly negative, consisting of 4260 glutamate residues and its exterior provides a suitable platform for conjugating cancer cell targeting agents. 43,46 …”