Enhancing Laser Lithotripsy via Nanoparticle Fine-Tuned NIR absorption

摘要 输尿管镜(URS)经激光碎石术(LL)是治疗尿路结石病(U.S.)的首选方法，这种疾病 这是美国第二昂贵的泌尿科疾病，每年的医疗支出超过20亿美元。这个 高功率/高频Ho(Ho)：YAG激光器和Tm光纤激光器的临床应用 (伦敦交通局)从根本上改变了LL的运作模式。与传统的分段模式不同， 相当大的碎片的篮子提取，当代LL通常使用粉尘和爆裂粉尘进行 将石块就地粉碎成灰尘而不需要提取碎片的模式。除尘的挑战 然而，目前的爆裂除尘有三个方面：1)作用机制还不完全清楚；2)爆裂除尘 最佳处理条件因石材成分不同而有很大差异，3)升温快 在高功率喷粉过程中产生。因此，有一种尚未满足的需求，即开发新的临床应用 能够提高处理效率的可部署技术，而不考虑石材成分， 缩短了手术时间，同时降低了肾组织损伤的风险。首要目标是 这份杜克大学泌尿外科前沿中心(P20)的申请是为了培养和支持职业生涯 徐宝春博士的发展，他是一位有前途的早期研究员，具有以下专业知识 纳米技术，但在美国和良性泌尿外科领域是新的。该中心的研究项目有三个 具体目标集中在：(1)开发吸收峰优化的生物安全纳米颗粒 Ho：YAGs激光器(=2.1m)和热释光(=1.94m)；(2)研究了纳米粒子增强POP的效应 基于水凝胶的肾脏模型中的除尘，以及(3)探索纳米颗粒增强的爆裂除尘的效果 在猪的模型中。该中心的行政核心有两个具体目标：(1)促进生产力 研究项目团队之间以及与更广泛的CAIRIBU研究社区之间的合作，以及(2) 促进和支持许博士的职业发展计划。此外，我们将利用这些知识， 最近在杜克大学LL上建成的P20探索中心积累的资源和经验(PI： 钟博士)，以及NIDDK CAIRIBU互动核心(PI：Penniston，PhD)和 哥伦比亚大学U54中心(共同PI：Barasch，PhD/MD)对猪模型肾损伤的评估。协同效应， P20 Forward计划创建的初步数据和知识将支持未来的R01应用 通过NIDDK CAIRIBU计划对纳米技术增强的法律知识和广泛的美元研究进行研究。

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.