Project Summary (30 lines max): The goals of this proposal are to develop a novel nanotechnology based treatment for kidney stones and also to support the career development of Ian Houlihan, PhD. in his research on developing nanotechnology based treatments for urological diseases. Research: Kidney stones are a common disease with reported poor stone free rates (as low as 40%) with current clinical methods of treatment which results in a high reoccurrence rate (~40%) of the disease. Current clinical treatments for this disease are not without drawbacks, with the major drawbacks being the use of radiation to visualize the stone, direct contact between laser fiber and the stone is required, and damage to surrounding tissue due to the high absorption of laser energy in the water region. With the new technology that is proposed here a number of these drawbacks can be addressed resulting in a safer and more effective treatment for the patient and clinician. This project will first investigate how this new technology causes stone comminution, this will be done by carrying out a baseline characterization of the nanomaterials and human kidney stones being used. This will inform what the minimum energy is required to cause stone breakdown and define the parameters needed for the in vivo application of this technology. It will also investigate the two predominant modes of failure with using these nanomaterials, this mechanism is believed to be a dual mode mechanism of photothermal and photoacoustic energy generated by the gold nanomaterials when irradiated with a near-infrared laser source. Secondly this project will develop stone targeting nanomaterials that will specifically bind to the kidney stone. These newly developed nanomaterials will be characterized and their ability to convert laser energy to heat and acoustic forms will be quantified. These targeting nanomaterials will be tested for safety in a number of different ways, firstly they will be tested for any toxic effects on urothelial cells, secondly they will be tested with an ex vivo porcine model to ensure they cause no adverse reactions to the kidney tissue, lastly these nanomaterials will be tested in a murine model to show their safety in an in vivo model. The last aim of this proposal is to conduct a pilot study on the efficacy of this technology in a porcine model. This new technology will be compared to the clinical gold standard, laser lithotripsy. The model will also be used to assess how effectively and safely our technology performs in a live animal. Career Development: The investigator has a technical background in engineering and experience in developing materials for medical applications and aims to use this award to help in learning new skills in developing and executing cellular and animal based studies for the development of new treatments for urological disease. The career development plan has a number of different courses specifically in learning about histopathology, biology...