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Photonic Lithotripsy: Utilizing Engineered Nanoparticles for Kidney Stone Fragmentation

By: Smita De, MD, PhD, Cleveland Clinic, Ohio, Lerner College of Medicine, Cleveland, Ohio | Posted on: 20 Jul 2023

Figure 1. Examples of human kidney stones before (top row) and after (bottom row) photonic lithotripsy. Engineered nanoparticles coating the stones were activated with a noncontact 785-nm laser at 2 W for 3 minutes from a distance of up to 2 cm. Some color changes in the treated stones are due to the color of the nanoparticle solution. PHF indicates polyhydroxy fullerenes.
Figure 2. Microcomputed tomography (microCT) and scanning electron microscopy (SEM) images of the same calcium oxalate stone before (left) and after (right) fragmentation with photonic lithotripsy using a noncontact 1,320-nm laser at 3.5 W. Note crack formation in the microCT images and restructuring of the stone surface in the SEM images after photonic lithotripsy.

I am honored to have been accepted into the AUA Urology Scientific Mentoring and Research Training (USMART) program and was delighted to meet my mentor, Dr Brant Inman from Duke University, in person at the 2023 AUA Annual Meeting in Chicago. As an endourologist, prostate enucleation enthusiast, and bioengineer, I have a large breadth of research interests relating to benign prostatic hyperplasia and kidney stones, with a strong focus in translational studies and novel technologies. One of my goals during this year in the USMART program is to work closely with Dr Inman to successfully pursue external funding to support my collaborative research project in developing a new technique for lithotripsy using nanotechnology.

Kidney stones affect almost 1 in 10 individuals in the US1 and are associated with significant morbidity and even mortality.2 Unfortunately, current surgical treatments for kidney stones have poor success rates and are associated with a number of risks.3 I have established a collaboration with Vijay Krishna, PhD, at Cleveland Clinic, an expert in nanomaterials, and we, along with our NIH training grant–funded postdoc, Ian Houlihan, PhD, have demonstrated the ability to fragment kidney stones in vitro using a novel technology called photonic lithotripsy. In photonic lithotripsy, kidney stones are coated with engineered nanoparticles, specifically polyhydroxy fullerenes (PHFs), which are activated by noncontact coherent light waves. The light activation, which can be performed with various low-intensity near-infrared lasers, causes the nanoparticles to produce tiny, localized vibrations or mechanical bursts that then fragment the kidney stones. During photonic lithotripsy, stones do not have to be touched or, potentially, even visualized. By creating the energy for stone fragmentation at the surface of the stone rather than the energy traveling through healthy tissue (like shock waves) or fragile ureteroscopes, photonic lithotripsy could possibly reduce procedure time and complexity, minimize risk of injury to tissues, improve surgeon ergonomics, increase surgical success rates, and decrease the need for radiation.

Using internal grant funding and philanthropic donations through the Cleveland Clinic Foundation, we have completed proof-of-concept studies showing successful stone fragmentation using photonic lithotripsy (examples shown in Figure 1). Deidentified human kidney stones were acquired from our pathology department after obtaining Institutional Review Board approval. We performed in vitro photonic lithotripsy by coating the stones with PHF nanoparticles and activating the PHFs using different combinations of near-infrared laser wavelengths, laser settings, and laser distances. All common stone types including calcium oxalate monohydrate, calcium oxalate dihydrate, calcium phosphate, and uric acid stones were successfully fragmented using low-intensity laser energy (2-3.5 W) at a distance of 1-2 cm. We have additionally performed scanning electron microscopy, microcomputed tomography, and Fourier transform infrared spectroscopy of stone specimens before and after photonic lithotripsy to characterize the mechanical and thermal effects during treatment (Figure 2).

Our team’s goal is to spend the next few years better understanding the mechanism of stone failure during photonic lithotripsy (ie, quantify mechanical energy produced by the nanoparticles and any thermal effects), optimizing its parameters, and performing animal studies to evaluate its safety and efficacy. We will also work on improving the efficiency of stone fragmentation through modification of the PHF nanoparticles to more strongly bind to specific types of stones.

I am excited to work with the AUA USMART program and my mentor on grant writing as well as developing preclinical trials to achieve the above objectives and my personal goal of becoming an independently funded surgeon-scientist. I believe that Dr Inman’s experience with extramural funding and translational research, specifically in nanotechnology, as well as his role on the editorial team for European Urology, will be highly advantageous throughout this process and for my overall career development.

We look forward to submitting the results of our studies to The Journal of Urology® for consideration for publication in the near future. Ultimately, our hope is that photonic lithotripsy may allow us to provide improved care and a better quality of life for our kidney stone patients as well as decrease the burden of kidney stone management on the health care system with fewer repeat surgeries or complications.

  1. Abufaraj M, Xu T, Cao C, et al. Prevalence and trends in kidney stone among adults in the USA: analyses of National Health and Nutrition Examination Survey 2007-2018 data. Eur Urol Focus. 2021;7(6):1468-1475.
  2. Darrad MP, Yallappa S, Metcalfe J, et al. The natural history of asymptomatic calyceal stones. BJU Int. 2018;122(2):263-269.
  3. Khan SR, Pearle MS, Robertson WG, et al. Kidney stones. Nat Rev Dis Prim. 2016;2:16008.

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