Enhancing Laser Lithotripsy via Nanoparticle Fine-Tuned NIR absorption

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ABSTRACT Ureteroscopy (URS) via laser lithotripsy (LL) is the treatment of choice for urinary stone disease (USD), which is the second most costly urologic condition in the US with an annual healthcare expenditure over $2 billion. The recent clinical introduction of high power/high frequency Holmium (Ho): YAG lasers and Thulium Fiber Laser (TFL) have fundamentally altered the mode of LL operation. Instead of the conventional fragmenting mode with basket extraction of sizable fragments, contemporary LL is often performed using dusting and pop-dusting modes that pulverize stone to dust in situ without the need for fragment extraction. The challenges in dusting and pop-dusting at present, however, are three-fold: 1) the mechanism of action is not fully understood, 2) the optimal treatment condition varies significantly with stone compositions, and 3) rapid temperature rise is produced during high power pop-dusting. Consequently, there is an unmet need to develop new and clinically deployable technologies capable of improving the treatment efficiency regardless of stone compositions, shortening the procedure time, while concomitantly lessening the risk of renal tissue injury. The overarching goal of this Duke University FORWARD Urology Center (P20) application is to foster and support the career development of Dr. Po-Chun Hsu, PhD who is a promising early-stage investigator with expertise in nanotechnology, yet new to the field of USD and benign urology. The Center's Research Project has three Specific Aims focusing on (1) Developing biologically safe nanoparticles with absorption peak optimized for Ho:YAG laser (=2.1 m) and TFL (=1.94 m); (2) Investigating the effects of nanoparticle-enhanced pop- dusting in a hydrogel-based kidney model, and (3) Exploring the effects of nanoparticle-enhanced pop-dusting in a porcine model. The Center's Administrative Core has two Specific Aims: (1) Facilitating productive collaborations among the Research Project Team and with the broader CAIRIBU research community, and (2) Fostering and supporting the career development plan for Dr. Hsu. Furthermore, we will leverage the knowledge, resources, and experience accumulated from a recently completed P20 exploratory center on LL at Duke (PI: Zhong, PhD), together with the support of the NIDDK CAIRIBU Interactions Core (PI: Penniston, PhD) and the Columbia U54 Center (co-PI: Barasch, PhD/MD) on assessment of renal injury in a porcine model. Synergies, preliminary data, and knowledge created by this P20 FORWARD program will support future R01 applications on nanotechnology-enhanced LL and the broad range of USD research through the NIDDK CAIRIBU program.