Modification of gold markers with Doxorubicin as Radiosensitizer encapsulated in sustained release PLGA nanoparticles to enhance Image Guided Radiotherapy (IGRT)

National Cancer Institute (NCI) predicts the number of cancer cases in United States alone by the year 2030 to be 2.3 million which is a 45% increase than the current 1.6 million. Therefore there is an undying need for research and development to aggressively attack this disease. Cancer is a multifaceted disease. So, there is no single approach to the treatment of this disease. Various expeditions have been undertaken in all directions to counter this deadly enemy.;Radiation therapy is one of these expeditions. X Rays were discovered by William Roentgen in 1895. The use of radiation therapy began in the same year when Emil Grubbe used X rays for breast cancer therapy. Radiation oncology has advances leaps and bounds in the last century. One of them was Image Guided Radiation therapy (IGRT). A tumor is often considered a moving target. Prostate cancer tumors change positions due to movements of the prostate gland. This often leads to radiations missing the desired target and affecting healthy tissue. To avoid this, (IGRT) was introduced where inert metallic markers were inserted into the organ to pin point the location of the tumor. In spite of success in targeting the tumor a major hurdle in radiation therapy is the ability of cancer cells to repair damaged DNA. This results in an increase in the cell survival and loss of sensitivity to radiation therapy. One way of countering this problem is use of radio sensitizing agents that block DNA repair and increase the sensitivity of tumor cells to radiations. In this study we aim to design a sustained release platform of doxorubicin that could be used as radiosensitizing tool in radiation therapy.;The long term aim of this study is to modify gold markers with Doxorubicin in order to form a sustained release platform as an adjunct therapy for radiation therapy. To achieve this, the coated gold markers will be first tested for their in vitro and in vivo drug release and cytotoxicity. Pegylated PLGA Nanoparticles loaded with doxorubicin were formulated as the drug carrier. The pegylated nanoparticles were tested for in vitro cytotoxicity. These were dispersed in chitosan (3% aqueous solution) and this slurry was coated on a gold fiducials. Drug loading in the nano particles was optimized and they were characterized for particle size, zeta potential and morphology. The optimized and characterized nanoparticle formulation was tested for release of free doxorubicin over time. The release of free doxorubicin from the coated fiducial over time was also measured. PC3 human prostate cancer cells and HeLa cells were cultured and intracellular delivery of nanoparticles was determined both qualitatively and quantitatively by fluorescence microscopy and fluorescence spectroscopy respectively.;Initially, fiducials coated with dox-PLGA nanoparticles were implanted inside tumors using a 16G needle. The purpose of doing so was to study the spatial distribution of doxorubicin as it was released over time. We were faced with the problem of interference by tissue autofluorescence. Therefore it was impossible to unmix tissue autofluorescence from the doxorubicin signal. To, eliminate this phenomenon; we formulated PLGA nanoparticles that encapsulated a special kind of dye. This dye had its peak excitation and emission in the Near Infrared Range (NIR). The dye chosen for this study was Cy 7.5, a cyanine dye. These nanoparticles were injected intratumorally and in vivo imaging was carried out.