Nanotechnology holds great promise for the early detection and treatment of cancer. The ability to both detect and follow the initiation and progression of cancer without biopsy, surgery, or other invasive techniques should lead to lower costs and higher quality of life. The goal of this proposal is to develop viral nanoparticles (VNPs) as platforms for combination tumor targeting and imaging agents in vivo. Our multidisciplinary team combines molecular biology, structure, chemistry and in vivo biology to attack this problem. In this proposal we will study two well-characterized viruses: a plant virus, cowpea mosaic virus (CPMV);and an insect virus, flockhouse virus (FHV). The accumulated knowledge of the structure, function, assembly, genome packaging, chemical attachment, and in vivo bioavailability of FHV and CPMV, developed in the co-investigators'laboratories, makes these viruses ideal candidates for such platform development. We will test the ability of tumor-specific VNPs to attack tumor cells in vitro and in vivo, and study mechanisms of uptake of VNPs into cells. We will also package anti-tumor compounds and inhibitory genes inside the particles to facilitate tumor destruction. Finally we will test the ability of our VNPs to detect and destroy tumors in vivo. These studies will make a significant contribution to the development of improved tumor targeting and imaging nanotechnologies.
| Plummer, Emily M; Manchester, Marianne (2013) Endocytic uptake pathways utilized by CPMV nanoparticles. Mol Pharm 10:26-32 |
| Koudelka, Kristopher J; Ippoliti, Shannon; Medina, Elizabeth et al. (2013) Lysine addressability and mammalian cell interactions of bacteriophage ? procapsids. Biomacromolecules 14:4169-76 |
| Daniel, Kevin B; Agrawal, Arpita; Manchester, Marianne et al. (2013) Readily accessible fluorescent probes for sensitive biological imaging of hydrogen peroxide. Chembiochem 14:593-8 |
| Plummer, Emily M; Thomas, Diane; Destito, Giuseppe et al. (2012) Interaction of cowpea mosaic virus nanoparticles with surface vimentin and inflammatory cells in atherosclerotic lesions. Nanomedicine (Lond) 7:877-88 |
| Hovlid, Marisa L; Steinmetz, Nicole F; Laufer, Burkhardt et al. (2012) Guiding plant virus particles to integrin-displaying cells. Nanoscale 4:3698-705 |
| Agrawal, Arpita; Manchester, Marianne (2012) Differential uptake of chemically modified cowpea mosaic virus nanoparticles in macrophage subpopulations present in inflammatory and tumor microenvironments. Biomacromolecules 13:3320-6 |
| Patti, Gary J; Yanes, Oscar; Shriver, Leah P et al. (2012) Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin. Nat Chem Biol 8:232-4 |
| Rhee, Jin-Kyu; Baksh, Michael; Nycholat, Corwin et al. (2012) Glycan-targeted virus-like nanoparticles for photodynamic therapy. Biomacromolecules 13:2333-8 |
| Huang, Rick K; Steinmetz, Nicole F; Fu, Chi-Yu et al. (2011) Transferrin-mediated targeting of bacteriophage HK97 nanoparticles into tumor cells. Nanomedicine (Lond) 6:55-68 |
| Steinmetz, Nicole F; Cho, Choi-Fong; Ablack, Amber et al. (2011) Cowpea mosaic virus nanoparticles target surface vimentin on cancer cells. Nanomedicine (Lond) 6:351-64 |
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