Viral nanoparticles as platforms for the design of novel targeted therapeutics

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Targeting therapies and imaging agents specifically to areas of disease in the body, while avoiding healthy tissue, is an important goal in biomedicine. This project focuses on the utilization of the well-characterized plant virus Cowpea mosaic virus (CPMV) as a platform for the design of novel "smart" targeted therapeutics. CPMV particles are naturally occurring, monodisperse, 30 nm-sized nanoparticles. The combined biodegradability, ease of production, and tunability make CPMV an excellent candidate for such platform development. The utility of multivalent fluorescent CPMV probes for vascular imaging in live animals has been demonstrated. More recently, we showed tumor homing of specifically targeted CPMV particles in preclinical animal models. The overall goal of this proposal is the development of 'smart' 3D nanodevices that interlink targeting. Imaging, and therapy. The first goal is to explore the potential of therapeutic CPMV formulations. I will use VNPs as a template for the constrained synthesis of iron oxide nanocrystals within the capsld interior for potential applications in hyperthermia treatment. Next, I will evaluate VNP-photosensitizer (fullerene) hybrid materials for photo-activated cancer therapy. In the second goal, to combine targeting, imaging, and therapy, will fabricate highly organized, controllable, and tunable VNPs networks consisting of various different "specialized" VNPs. Such complex formulations are expected to overcome limitations of single VNPs and would allow i) targeting to several molecular receptors thus increasing tumor homing efficiency, and ii) delivery of different therapeutics, which is expected to increase therapeutic success. Cancer is a complex endeavor and i stronly believe that such multicomponent formulations may serve as promising candidates for novel targeted therapies. During my pre-doctoral training 1 have learned to tailor VNPs and to fabricate nanostructured matenals. My post-doctoral training has provided expertise in in vitro and in vivo models. This puts me in a unique position of being able to create nanomaterials, but also to study their in vivo properties.