Funds are requested to develop a nanovehicle that can be easily modified for the targeted treatment and imaging of solid tissue tumors. We have taken advantage of the strong non-covalent interaction between biotin and avidin to design the platform and its applications. The multi-purpose nanoparticles (NP) are assembled with a paramagnetic core to facilitate magnetic resonance imaging (MRI) and a gold coating to which thiolpoly(ethylene glycol)-biotin (PEG) is attached. Neutravidin is linked to the biotin terminus o the PEG to provide multivalent attachment sites for additional biotinylated molecules in different combinations. Targeting of the nanoplatform is achieved by monoclonal antibodies (mAb) directed against tumor-specific biomarkers. The flexibility of assembly allows for various antibodies and/or anti-tumor therapeutics to be exchanged without the need to synthesize the nanovehicle from scratch for each application. The nanovehicle can be adapted based upon biopsy assay for loss of antibody target and/or resistance to chemotherapy during tumor progression. The bulk of the project will be directed towards assessing and optimizing these bioconjugates in vitro before moving to an in vivo system. The specificity and level of cellular uptake will be thoroughly validated. As a proof-of-concept we have developed our NP to target pancreatic adenocarcinoma with boron neutron capture therapy (BNCT). The in vivo model we have selected for the eventual test of these NPs is the bird chorioallantoic membrane (CAM) carrying human tumor xenografts. As a prelude to these in vivo studies, a quail ex ovo CAM system carrying our NPs has been developed for MR imaging in the Wellesley College micro-MRI system.
Funds are requested to develop a multi-purpose nanovehicle for targeted boron neutron capture therapy and imaging of cancers. The novelty to easily change the targeting antibody as well as the anti-tumor therapeutic payload provides for personalized treatment when a tumor becomes chemo-resistant or targeting is diminished.
