Project Summary Urinary (kidney) stone disease is common and affects about 1 in 11 people in the United States, costing > $2 billion in healthcare expenditures per year in the United States. Current endoscopic surgical treatment of urinary stone disease is centered around ureteroscopic laser lithotripsy to fragment the stone into smaller parts. The fragments are either actively retrieved from the body one by one with a wire basket or left to pass spontaneously. Depending on the size of the stone fragments, the process can be inefficient, tedious, and time-consuming in the operating room which is expensive. Rendering a patient stone-free is the best way to prevent further complications or repeat interventions due to residual stone fragments, yet current stone-free rates only approach 60-75%. The long-term goal is to improve clinical outcomes by achieving higher stone-free rates in a shorter amount of time. The objective of this R21 application is to develop, characterize, and test the feasibility of a novel magnetic-based technology to improve kidney stone fragment retrieval. We propose MagSToNE (Magnetic System for Total Nephrolith Elimination), a new approach based on magnetic nanotechnology for efficient stone fragment retrieval. MagSToNE consists of a flexible magnetic wire with a biocompatible plastic sheath, and superparamagnetic particles which are functionalized to bind to kidney stones. The magnetic wire is compatible with standard ureteroscopes and is similar in size to the guidewires routinely used in ureteroscopy. It is additionally uniquely designed to generate much stronger magnetic field gradients than a typical magnet. After laser fragmentation of a kidney stone, stone fragments are coated with magnetic nanoparticles which have been functionalized to bind to kidney stones. The stones can then be easily retrieved en masse by the magnetic wire, improving the efficiency of stone clearance compared to the conventional wire basket. This technology will be developed through the following specific aims: (1) to develop and optimize the superparamagnetic particles and magnetic wire to capture and retrieve stone fragments; and (2) to compare the performance of MagSToNE to conventional stone retrieval methods, with in vivo feasibility and biodistribution/toxicity studies in a porcine model. This project is innovative in that it shifts the paradigm of stone clearance from one based purely on mechanical retrieval to one that utilizes attractive magnetic forces and promises better performance. The proposed research is significant because it has the potential to substantially improve clinical outcomes and reduce healthcare costs related to kidney stone surgery.