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      Gold nanoshell-localized photothermal ablation of prostate tumors in a clinical pilot device study

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          Prostate cancer is the most common nonskin cancer in the United States, where approximately 1 in 9 men will be diagnosed in their lifetime. The prostate is near several vital structures, such as the urethra and neurovascular bundle, and whole gland treatments for prostate cancer can disrupt normal urinary, bowel, and sexual functioning. Here we report the initial results of a clinical trial for nanoparticle-based photothermal cancer therapy. The trial was designed to perform ultrafocal photothermal ablation of cancerous tumors within the prostate. Gold-silica nanoparticles designed to absorb near-infrared light at wavelengths of high tissue transparency provide a highly localized light-based strategy for the treatment of prostate cancer, with substantially reduced risks for deleterious treatment-related side effects.


          Biocompatible gold nanoparticles designed to absorb light at wavelengths of high tissue transparency have been of particular interest for biomedical applications. The ability of such nanoparticles to convert absorbed near-infrared light to heat and induce highly localized hyperthermia has been shown to be highly effective for photothermal cancer therapy, resulting in cell death and tumor remission in a multitude of preclinical animal models. Here we report the initial results of a clinical trial in which laser-excited gold-silica nanoshells (GSNs) were used in combination with magnetic resonance–ultrasound fusion imaging to focally ablate low-intermediate-grade tumors within the prostate. The overall goal is to provide highly localized regional control of prostate cancer that also results in greatly reduced patient morbidity and improved functional outcomes. This pilot device study reports feasibility and safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate cancer. After GSN infusion and high-precision laser ablation, patients underwent multiparametric MRI of the prostate at 48 to 72 h, followed by postprocedure mpMRI/ultrasound targeted fusion biopsies at 3 and 12 mo, as well as a standard 12-core systematic biopsy at 12 mo. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients, with no significant difference in International Prostate Symptom Score or Sexual Health Inventory for Men observed after treatment. This treatment protocol appears to be feasible and safe in men with low- or intermediate-risk localized prostate cancer without serious complications or deleterious changes in genitourinary function.

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          Most cited references 28

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          Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance.

          Metal nanoshells are a class of nanoparticles with tunable optical resonances. In this article, an application of this technology to thermal ablative therapy for cancer is described. By tuning the nanoshells to strongly absorb light in the near infrared, where optical transmission through tissue is optimal, a distribution of nanoshells at depth in tissue can be used to deliver a therapeutic dose of heat by using moderately low exposures of extracorporeally applied near-infrared (NIR) light. Human breast carcinoma cells incubated with nanoshells in vitro were found to have undergone photothermally induced morbidity on exposure to NIR light (820 nm, 35 W/cm2), as determined by using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of NIR illumination. Likewise, in vivo studies under magnetic resonance guidance revealed that exposure to low doses of NIR light (820 nm, 4 W/cm2) in solid tumors treated with metal nanoshells reached average maximum temperatures capable of inducing irreversible tissue damage (DeltaT = 37.4 +/- 6.6 degrees C) within 4-6 min. Controls treated without nanoshells demonstrated significantly lower average temperatures on exposure to NIR light (DeltaT < 10 degrees C). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining, which are indicators of irreversible thermal damage. Control tissues appeared undamaged.
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            Nanoshell-enabled photonics-based imaging and therapy of cancer.

            Metal nanoshells are a novel type of composite spherical nanoparticle consisting of a dielectric core covered by a thin metallic shell which is typically gold. Nanoshells possess highly favorable optical and chemical properties for biomedical imaging and therapeutic applications. By varying the relative the dimensions of the core and the shell, the optical resonance of these nanoparticles can be precisely and systematically varied over a broad region ranging from the near-UV to the mid-infrared. This range includes the near-infrared (NIR) wavelength region where tissue transmissivity peaks. In addition to spectral tunability, nanoshells offer other advantages over conventional organic dyes including improved optical properties and reduced susceptibility to chemical/thermal denaturation. Furthermore, the same conjugation protocols used to bind biomolecules to gold colloid are easily modified for nanoshells. In this article, we first review the synthesis of gold nanoshells and illustrate how the core/shell ratio and overall size of a nanoshell influences its scattering and absorption properties. We then describe several examples of nanoshell-based diagnostic and therapeutic approaches including the development of nanoshell bioconjugates for molecular imaging, the use of scattering nanoshells as contrast agents for optical coherence tomography (OCT), and the use of absorbing nanoshells in NIR thermal therapy of tumors.
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              Plasmon Resonance Shifts of Au-CoatedAu2SNanoshells: Insight into Multicomponent Nanoparticle Growth


                Author and article information

                Proc Natl Acad Sci U S A
                Proc. Natl. Acad. Sci. U.S.A
                Proceedings of the National Academy of Sciences of the United States of America
                National Academy of Sciences
                10 September 2019
                26 August 2019
                26 August 2019
                : 116
                : 37
                : 18590-18596
                aDepartment of Urology, Icahn School of Medicine at Mount Sinai , New York, NY 10029;
                bDepartment of Radiology, Icahn School of Medicine at Mount Sinai , New York, NY 10029;
                cClinical Research, Nanospectra Biosciences , Inc., Houston, TX 77054;
                dDepartment of Urology, McGovern Medical School at the University of Texas Health Science Center at Houston , Houston, TX 77030;
                eDepartment of Urology, Michigan Medicine University of Michigan , Ann Arbor, MI 48109;
                fDepartment of Biomedical Engineering, Duke University , Durham, NC 27708;
                gLaboratory for Nanophotonics, Rice University , Houston, TX 77005
                Author notes
                1To whom correspondence may be addressed. Email: art.rastinehad@ 123456mountsinai.org or halas@ 123456rice.edu .

                Edited by Catherine J. Murphy, University of Illinois at Urbana–Champaign, Urbana, IL, and approved July 25, 2019 (received for review April 23, 2019)

                Author contributions: A.R.R. invented the transperineal MR US fusion guided gold nanoshell excitation technique used in the trial; A.R.R., J.A.S., J.L.W., and N.J.H. designed research; A.R.R., H.A., E.W., J.S.W., J.P.S., S.K.D., M.R.C., C.J.K., B.T., S.C.L., A.K.T., J.A.S., S.E.C., A.K.G., J.L.W., and N.J.H. performed research; J.A.S., J.L.W., and N.J.H. contributed new reagents/analytic tools; A.R.R., H.A., E.W., J.S.W., J.P.S., S.K.D., M.R.C., C.J.K., B.T., S.C.L., A.K.T., S.E.C., and A.K.G. analyzed data; and A.R.R., H.A., E.W., J.S.W., J.P.S, S.K.D., M.R.C., C.J.K., B.T., S.C.L., A.K.T., J.A.S., S.E.C., A.K.G., J.L.W., and N.J.H. wrote the paper.

                Copyright © 2019 the Author(s). Published by PNAS.

                This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).

                Page count
                Pages: 7
                Funded by: Welch Foundation 100000928
                Award ID: C-1220
                Award Recipient : Naomi J. Halas
                Biological Sciences
                Medical Sciences


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