Our goal is to create a nanotherapeutic agent that will target pancreatic cancer cells, serve as a vehicle for radiative therapy, and enable noninvasive imaging using MRI. To optimize the particles, we are concurrently investigating the behavior of protein-conjugated gold nanoparticles in protein-rich environments, modeling conditions within the human body.<br/>Our proposed nano-vehicle consists of an iron core for tracking with MRI and a gold shell to which we can attach various decorations: stealth-coating polymers, antibodies, and a polymer loaded with 10B for boron nuclear-capture therapy. Herein, we report results with pure gold nanoparticles (AuNPs), which serve as a simple model. Nanoparticles are coated in thiol-terminated poly(ethylene glycol) (PEG), some of which are biotin-terminated. Biotin-avidin interactions are used for the conjugation of antibodies and boron-10 rich polymers to our nanoparticle. Two antibody conjugation schemes have been successful in this study, and conjugating 10B-rich polymers is underway. With progress made in the construction of this nanovehicle, we are also testing the stability of these nanoparticles in the presence of proteins. This project evaluates the protein resistance of two types of polymer coatings: PEG and PEK. PEK is a peptidic polymer with an alternating sequence of five glutamic acid and four lysine units. To probe protein interaction, samples of AuNPs coated with PEG or PEK were synthesized and then characterized with UV-visible spectroscopy, dynamic light scattering, and Zeta-potential to monitor size, charge, and extent of aggregation. Protein resistance was evaluated by incubating each type of coated AuNPs with negatively-charged bovine serum albumin (BSA) and with positively-charged lysozyme. We found that stealth-coating the AuNPs minimizes protein adsorption and increases biocompatibility of the nano-vehicle. Further studies investigating protein adsorption to nanoparticles with directionally conjugated antibodies, BSA competition with stealth coating, and the impact of polymer chain adjustments to adsorption resistance are underway.

Investigating the integrity of novel nanovehicles for targeting pancreatic cancer

249th National Meeting (2015)

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