Project Outline

Abstract

In current research, gold nanoparticles have been identified as effective bio-sensing substrates, as well as effective drug vectors, partly due to their inherent biocompatibility. This project utilizes gold nanoparticles as a basis for a multi-functionalized payload vector for oncologic radiotherapy. Starting with a 5 nm gold core, alternating layers of cationic polyelectrolyte (4-Borono-L-Phenylalanine-Poly(fluorescein isothiocyanate allylamine) hydrochloride (BPA:FITC-PAH)) and anionic polyelectrolyte (4-Borono-L-Phenylalanine-Poly(4-styrene sulfonate) (BPA:PSS)) are electrostatically deposited onto the nanoparticle surface. Finally, folic acid is electrostatically functionalized to the surface of the layered particle.

Separately, tensegrity DNA Origami structures are synthesized, and then "walked" over a 150 nm by 100 nm flat DNA Origami tile. During "walking", the tensegrity structures have a biotinylated DNA cargo conjugated onto one of their three available binding sites. The tensegrity structures are then attached to the layered gold nanoparticle (LGNP) through an EDC-sulfo-NHS coupling method. The final product is a gold nanoparticle, layered with boron-containing polyelectrolytes, and functionalized with DNA tensegrity structures hosting biotinylated DNA. Biotinylated DNA was used in this project as a proof-of-concept for a true cancer-targeting agent; in a clinical setting, a cancer targeting agent would be substituted. In practice, this system would selectively bind to the surface of cancer cells. It would then undergo cell uptake and be subsequently irradiated with a neutron beam. This induces a decay reaction between the boron and thermal neutrons, which releases a lethal dose of energy in approximately the diameter of the cell. Lastly, the gold nanoparticle core acts as an MRI contrast enhancer to actively track the progress of oncological treatment. Therefore, the proposed system actively targets and kills cancer cells while leaving healthy cells unharmed.


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