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Objective To determine whether photothermal polymer nanoparticles (NPs) can interface with bacteria associated with kidney stones, generate heat when stimulated with near infrared (NIR) light, and aid in reducing bacterial burden. Methods Two types of kidney stones, artificial, and those removed during percutaneous nephrolithotomy (PCNL), were inoculated with Escherichia coli (E. coli) and then incubated with NPs composed of FITC-labeled Poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b′]-dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe). Association of the PCPDTBSe NPs was evaluated using fluorescence microscopy. Infected stones were incubated with NPs and exposed to 800 nm light to generate temperature increases from 25.4 to 68.6 °C on the stones. Following photothermal treatment, the stones were homogenized and the bacteria was enumerated via colony counting assays to evaluate the bactericidal effect. The photothermal effect was also evaluated using scanning electron microscopy of the treated biofilms. Results Both kidney stone types sequestered E. coli. Control stones and stones treated with laser only had growth of numerous bacterial colonies, while stones exposed to NPs and laser grew significantly less, or none (p = 0.02). Conclusions The polymer NPs interface with E. coli on artificial and patient-derived kidney stones, and they can impart a bactericidal effect, when stimulated with NIR to generate heat. This technique may possibly be extended to treating infected kidney stones in patients.

Introduction Metastatic colorectal cancer (CRC) is complicated by chemotherapy-resistant cell populations. Oxaliplatin is used in heated intraperitoneal hyperthermic chemoperfusion (HIPEC) for treatment of disseminated CRC. Photothermal nanoparticles can provide focal heating to improve the response of CRC cells to oxaliplatin, by confining heating near individual cells. Reduction in cellular luciferase signal may allow single-cell-resolution recording of thermal dosimetry. Methods Oxaliplatin resistant (OxR) variants of luciferase-expressing CT26.WT-Fluc-Neo CRC cells were developed and their sensitivity to hyperthermia was evaluated. Polymer-based photothermal nanoparticles were developed, characterized and used to explore their potential for imparting a thermal dose to improve cell response to oxaliplatin. A correlation of thermal dose to intracellular luciferase activity was established using quantitative luminescence monitoring and microscopy. Results Luciferase-based monitoring of thermal dose within CT26 cell lines was validated within the ranges of 0.04–8.33 CEM43 for parental cells and 0.05–9.74 CEM43 for OxR CT26 cells. This was further confirmed using nanoparticle-induced hyperthermia, where the single-cell resolution of the thermal dose can be achieved. The nanoparticles enhance cell killing of resistant cells when combined with oxaliplatin and stimulated to generate heat. Conclusion Nanoparticle-based hyperthermia is effective for augmenting chemotherapy and can be coupled with reductions in CT26 luciferase expression to monitor thermal dose at single-cell resolution. The development of OxR CT26.WT-Fluc-Neo CRC cells sets the stage for pre-clinical evaluations to measure nanoparticle-induced hyperthermia to augment chemotherapy (Nano-HIPEC) in a chemotherapy-resistant model of disseminated CRC.