| Breast cancer is the second most common cancer next to skin cancer. There are 212,920 new cases and 40,970 deaths in United States in 2006 according to American Cancer Society. Tumors have unorganized vasculature, and therefore, tend to accumulate hemoglobin, which is a natural strong near infrared (NIR) absorbers in tissue. Breast tumors have, therefore, approximately 4 times higher absorption than breast tissue. Optical mammography by NIR light can be an effective approach, especially for younger women (<40 years), for whom X-rays show low sensitivity due to their dense breast tissue, and, it is safe for pregnant women who cannot undergo ionizing radiation, such as X-ray.;For detecting small and deeply seated tumors by NIR, optical contrast agents can enhance the sensitivity. Indocyanine green (ICG, FDA approved contrast agent), nanogold particles (NGPs), Fe3O4 nanoparticles, and gold coated Fe3O4 nanoparticles were tested for their effectiveness as optical contrast agents. For this study to test the effectiveness of these contrast agents, an experiment tumor model, i.e., a vitamin E capsule shell (1.5 x 1 x 1 cm) filled with a contrast agent, was placed in an experimental breast tissue model at various depths. The surface of the breast tissue model was then scanned by NIR at a wavelength of 780 nm. ICG at a concentration of 30 muM showed the contrast in absorption of twice and fluorescence of 7 times higher than the tumor model without a contrast agent. NGP at 0.01% was able to detect the tumor model even at 2.5 cm deep (deepest in our model), indicating NGP is an effective optical contrast agent. NGPs are also known to enhance fluorescence significantly when they are linked to fluorophores at a particular distance. Cypate, a derivative of ICG, linked NGPs via streptavidin spacer (∼3 nm) have shown the fluorescence contrast 100% higher than Cypate alone, in our experimental breast tissue model system.;Low heat (42∼45°C) hyperthermia can induce slow cell death by deactivating enzymes in tissue. Magnetic nanoparticles, such as Fe3O 4, are heated by a well selected alternating electromagnetic (AEM) frequency. At a frequency of 450 KHz, Fe3O4 nanoparticles at a size of 10∼30 nm were heated effectively, without heating the tissue components. Gold was coated onto Fe3O4 nanoparticles to enhance the NIR contrast as well as keeping the particle property for hyperthermia. The heating of gold coated (layer thickness: 4∼7 nm) Fe3O 4 nanoparticles (20∼30 nm) was similar to that of Fe3O 4 nanoparticles without the gold layer. At a concentration of 0.01wt%, gold coated Fe3O4 nanoparticles significantly enhanced the absorption contrast by 3 dB.;Nanoparticles functionalized with tumor specific biomolecules can enhance their tumor targetability. Luteinizing hormone releasing hormone (LHRH) is a hormone of 10 amino acid peptide. LHRH receptors are over expressed in approximately 50% of breast cancer cells but only a few normal organs express the receptor. The binding affinity of LHRH linked NGPs was examined in the mouse gonadotrope cell-line that expresses high levels of LHRH receptor. The binding affinity of LHRH linked NGPs was found to be similar to LHRH alone up to LHRH concentration of 0.1 nM. Then, LHRH linked Fe3O4 nanoparticles were reacted with human breast cancer cells (MCF-7) for hyperthermia study. After washing out the unbound particles, the cells were exposed to AEM field at a frequency of 400 KHz and a power of 3 KW, for 15 min. Approximately 90% of cells treated with LHRH-Fe3O4 nanoparticles were killed, while most cells treated with Fe3O4 nanoparticles without LHRH remained alive.;Our study results showed that Cypate, gold coated Fe3O 4 nanoparticles, and LHRH have a potential to be a basis for a multi-functional nano-entity with the propertiy of tumor specific, optical contrast enhancing magnetic nanoparticles for cancer detection and treatment. |
