UC Riverside

The use of nanosized materials for the diagnosis and treatment of disease has grown exponentially in recent years. Biologically derived materials, more specifically, plant virus constructs offer several advantages as tools for nanomedicine including the ability to self-assemble into highly monodisperse structures with discrete shape and size containing highly addressable surfaces for chemical or biological modification. NIR dye encapsulating nanoconstructs have demonstrated their importance as effective agents for deep tissue optical imaging in the early detection of cancers allowing for the visualization of small (>5mm) tumors. Encapsulation mitigates the deficiencies of organic NIR dyes by shielding them, increasing chemical and photostability, while decreasing clearance rates, and making hydrophilicity issues irrelevant. The objective of this study is to investigate the effectiveness of an optical nano-structured system for targeted near infrared (NIR) imaging of ovarian cancer cells that over-express the human epidermal growth factor receptor 2 (HER2), an important biomarker associated with ovarian cancer. The nano-structured system, optical viral ghosts (OVGs), is comprised of the genome-depleted plant-infecting brome mosaic virus (BMV) doped with NIR chromophore, indocyanine green (ICG), and functionalized at the surface by covalent attachment of monoclonal antibodies against the HER2 receptor. We use absorption, fluorescence spectroscopy, and dynamic light scattering to characterize the physical properties of the constructs. Using fluorescence imaging and flow cytometry, we demonstrate the effectiveness of these nano-structures for targeted NIR imaging of HER2 receptors in vitro. After demonstrating the effectiveness of these ICG doped nano-constructs in-vitro we investigate their payload flexibility and their potential for in-vivo use. Optimized fabrication parameters for the loading of two organic NIR dyes (ICG and BrCy-106) were established based on ϕ-value (ratio of capsid protein concentration: dye concentration) to produce nano-structures with the highest fluorescence emission. Despite the lack of specific targeting moieties OVGs localized to ovarian cancer nodules in nu/nu mice in-vivo more successfully than the corresponding unloaded dye. Ovarian cancer remains the dominant cause of death due to malignancies of the female reproductive system. The capability to identify and remove all tumors during intraoperative procedures may ultimately reduce cancer recurrence, and lead to increased patient survival. Our virus-resembling nano-structures could potentially be used for early detection and fluorescence guided cytoreduction surgery.