Gold nanoparticles have been increasingly used for biomedical applications, including imaging, drug delivery, and photothermal cancer therapy. The high surface to volume ratio of nanoscale materials allows for the loading of many drug molecules or targeting ligands onto each nanoparticle while using minimal gold concentrations, which helps to reduce deleterious side effects. The plasmonic properties of the gold nanoparticles, namely their strong light scattering and absorption properties, also make them highly suitable as imaging probes. To improve the design of gold nanoparticles for these applications, significant work has been done to better understand how varying their physical and surface chemical properties affect their interactions in biological environments. For example, the size of nanoparticles has been shown to influence their cellular uptake, with ~30 – 40 nm gold nanoparticles showing the highest rates of endocytosis. The surface chemistry (e.g. targeting peptides, proteins, drug molecules, etc.) of nanoparticles has also been shown to affect their rate of localization within cells and their toxicity. However, little is known about the interaction of nanoparticles with the cell nucleus, which stores genetic information and controls the life and death of the cell. This work will study how the size and shape of nuclear-targeted gold nanoparticles affects their uptake into cell nuclei, their interactions with DNA, and their cytotoxicity. Ultimately, the level of nuclear uptake will be correlated to the effectiveness of treatments such as drug delivery or photothermal cancer therapy, which relies on rapid heat production from localized gold nanoparticles to induce apoptotic cell death.
