Viral nanoparticles as platforms for the design of novel targeted therapeutics

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DESCRIPTION (provided by applicant): Targeting therapies and imaging agents specifically to areas of disease in the body, while avoiding healthy tissue, is an important goal in biomedicine. In this project the well-characterized plant virus Cowpea mosaic virus (CPMV) will be utilized as a platform for the design of novel "smart" targeted therapeutics. The combined knowledge of structure, function, assembly, and in vivo properties such as bioavailability make CPMV an excellent candidate for such platform development. The utility of multivalent fluorescent CPMV probes for vascular imaging in live animals was demonstrated. The goals of this proposal are first, to understand the fundamental mechanisms for targeting viral nanoparticles (VNPs) in vivo. I will examine whether the multivalent display of endothelial targeting peptides will allow to specifically target CPMV sensors to tumor-vasculature and/or tumor cells. The second goal is to explore the potential of therapeutic VNP formulations. I will evaluate the potential of doxorubicin-loaded CPMV formulations for cancer therapies. A second strategy will use VNPs as a template for the constrained synthesis of iron oxide nanocrystals within the capsid interior for potential applications in hyperthermia treatment. In a third approach I will evaluate VNP-fullerene hybrid materials for photo-activated cancer therapy. Last but not least, to combine targeting, imaging, and therapy, I will design and fabricate highly organized, controllable, and tunable VNPs networks consisting of various different "specialized" VNPs. This complex formulation is expected to overcome limitations of single VNPs My long-term goal is to utilize VNPs in combination with other nanomaterials or devices to study in vivo processes and to utilize nanomaterials as platforms for the development of "smart" targeted therapies. During my pre-doctoral training I have learned to chemically tailor VNPs and to fabricate nanostructured materials. I only have basic knowledge in in vitro and in vivo techniques. To fill this gap I have joined Prof. Manchester's laboratory at The Scripps Research Institute. With the expertise and the great facilities at TSRI, I will be able to fill this gap. This will put me in a unique position of being able to create and design nanomaterials, but also to study their in vivo properties. RELEVANCE: Cancer is causing substantial death and disabilities all over the world. Chemotherapy is generally not targeted and therefore many adverse side effects occur. Specifically targeted therapies would increase efficiency and result in fewer side effects, and thus improve quality of life. This project will help to understand how to build a complex network that combines several features including targeting and therapy in one therapeutic formulation for treatment.