Cancer is the second-most leading cause of death in the United States, with 1.66 million new cases expected to be diagnosed and over 580,000 Americans expected to die of cancer in 2013 alone. (American Cancer Society 2013) Current treatments result in damage to the healthy tissues and incomplete resections of solid tumors, but by harnessing nanotechnology, more effective treatments can be constructed. Gold nanoshells present a promising option for targeted cancer therapy. The anatomy of tumors causes the “enhanced permeability and retention” effect, which means that nano-scale particles will extravasate from the bloodstream and accumulate in the tumors. However, small nanoparticles must still diffuse from the tumor vasculature into the tumor tissue. Due to impaired vascularization, the particles are unable to reach into the entire tumor region. The purpose of our project is to create a “two-layer” nanoshell coated with alkanethiol and phosphatidlycholine and a “three-layer” nanoshell that coats the “two-layer” system with a layer of high-density lipoprotein. It is proposed that these coatings will allow for better penetration of solid tumors compared to the standard nanoshells modified with poly(ethylene glycol) (PEG). In addition to the nanoshells, citrate-gold nanoparticles were investigated as a control. Size, zeta potential, and morphology were optimized, and the penetration of the particles into solid tumors was investigated using dark-field microscopy. It was discovered that the “two-layer” nanoshells exhibited significantly more uptake into the solid tumors compared to PEGylated nanoshells, and should be further investigated as a platform for targeted cancer therapies.
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Development of novel layered nanoparticles for more efficient cancer treatment.
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