Enhancing Laser Lithotripsy via Nanoparticle Fine-Tuned NIR absorption

摘要 通过激光碎石术（LL）进行输尿管镜检查（URS）是泌尿系结石疾病（USD）的首选治疗方法， 这是美国第二昂贵的泌尿系统疾病，每年的医疗保健支出超过20亿美元。的 高功率/高频钬（Ho）：YAG激光器和钍光纤激光器的最新临床介绍 (TFL)从根本上改变了LL的运行模式。代替传统的分段模式， 篮式提取相当大的碎片，当代LL通常使用撒粉和爆粉进行 在不需要碎片提取的情况下，将石头就地粉碎的模式。除尘方面的挑战 然而，目前流行的粉尘有三个方面：1）作用机制尚未完全了解，2） 最佳处理条件因石材成分而异，3）快速升温， 是在大功率爆破除尘过程中产生的因此，存在开发新的且临床上有效的药物的未满足的需求。 能够提高处理效率而与结石成分无关的可部署技术， 缩短手术时间，同时降低肾组织损伤的风险。总体目标 这个杜克大学前进泌尿外科中心（P20）的应用是促进和支持的职业生涯 博士的发展Po-Chun Hsu，博士谁是一个有前途的早期研究者与专业知识， 纳米技术，但新的USD和良性泌尿学领域。该中心的研究项目有三个 具体目标集中于（1）开发具有针对以下目的优化的吸收峰的生物安全纳米颗粒： Ho：YAG激光（λ =2.1 μ m）和TFL（λ =1.94 μ m）;（2）研究纳米颗粒增强的pop- 在基于水凝胶的肾脏模型中撒粉，以及（3）探索纳米颗粒增强的弹出撒粉的效果 在猪模型中。中心的行政核心有两个具体目标：（1）促进生产力 研究项目团队之间的合作，并与更广泛的CAIRIBU研究社区，和（2） 促进和支持徐博士的职业发展计划。此外，我们将利用知识， 资源，以及最近在杜克完成的LL P20探索中心积累的经验（PI： Zhong，PhD），以及NIDDK CAIRIBU互动核心（PI：Penniston，PhD）和 哥伦比亚U 54中心（共同主要研究者：Barasch，PhD/MD）在猪模型中评估肾损伤。协同增效， P20 FORWARD计划产生的初步数据和知识将支持未来的R 01应用 通过NIDDK CAIRIBU计划，在纳米技术增强的LL和广泛的USD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.