This study aims to assess the risk of high intensity focused ultrasound (HIFU) therapy on the incidence of distant metastases and to investigate its association with HIFU-elicited anti-tumor immunity in a murine melanoma (B16-F10) model. Tumor-bearing legs were amputated immediately after or 2 days following HIFU treatment to differentiate the contribution of the elicited anti-tumor immunity. In mice undergoing amputation immediately after mechanical, thermal, or no HIFU treatment, metastasis rates were comparable (18.8%, 13.3% and 12.5 %). In contrast, with a 2-day delay in amputation, the corresponding metastasis rates were 6.7%, 11.8% and 40%, respectively. Animal survival rate was higher and CTL activity was enhanced in the HIFU treatment groups. Altogether, our results suggest that HIFU treatment does not increase the risk of distant metastasis. Instead, HIFU treatment can elicit an anti-tumor immune response that may be harnessed to improve the overall effectiveness and quality of cancer therapy. KeywordsHigh intensity focused ultrasound; metastasis; anti-tumor immunity; bioluminescent imaging; melanoma High-intensity focused ultrasound (HIFU) has recently emerged as a promising treatment modality for localized solid malignancies [1]. HIFU therapy has the unique advantage of being noninvasive and easily tolerable by the patient, thus allowing for repeated treatments. Despite this, there has been a long-standing concern regarding whether HIFU-induced mechanical damage may lead to the dissemination of cancer cells into the blood circulation, and thus promoting distant metastasis. Several groups have investigated the potential risk of metastasis induced by HIFU using animal models, but the results are contradictory [2;3;4;5]. Further, a recent clinical study has demonstrated no apparent increase in the number of patients with detectable circulating tumor cells following HIFU treatment, compared to the non-HIFU group [6].In early clinical applications, HIFU therapy was aimed to produce thermal coagulative necrosis of the tumor while avoiding the induction of cavitation bubbles [7]. This is because of the Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Materials and Methods AnimalsC57BL/6 female mice, 5-8 weeks old, were purchased from the Jackson Laboratory (Bar Harbor, ME) and handled in accordance with the established animal care policy. All animal studies were approved by the Duke University Institutional Animal Care & Use Committee. Tumor modelMurine melanoma cell line (B16-F10-Luc-G5) with stably transduced firefly luciferase gene was pur...

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Aggregation-caused quenching of carbon dots (CDs) has limited their application for optoelectronic devices. In this work, we reported a highly luminescent solid-state CDs through a freeze-drying assisted hydrothermal method, using citric acid, urea and boric acid as raw materials. The hydrothermal process triggers the formation of the carbonaceous structures, and freeze-drying treatment results in the dehydration and crossing linking reactions between the carbonaceous structures and boric acid, forming CDs embedded in the matrix of boric acid. Steady-state fluorescence spectra and timeresolved PL decay curves, together with the XPS data suggest the significant promotion of photoluminescence quantum yield after processing CDs from solution to powder state is attributed to surface passivation and activating of new emissive states caused by the attraction of boron. The CDs shows a high photoluminescence quantum yield of 80.1 %, with an excellent thermal stability, which are further used as phosphor for fabricating LED. A white LED is obtained after combining blue emissive CDs with orange emissive Cu nanocluster with UV-LED chips, achieving a high color rendering index of 89, and a Commission Internationale de L'Eclairage chromaticity coordinates of (0.33, 0.32).