Single agent nanoparticle for radiotherapy and radio-photothermal therapy in anaplastic thyroid cancer |
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| Affiliation: | 1. Department of Radiotherapy and Oncology, Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany;2. German Cancer Research Center (DKFZ), Heidelberg, Germany;3. German Cancer Consortium (DKTK) partner site: Frankfurt, Germany;4. Fraunhofer-Institute for Molecular Biology and Applied Ecology, Department of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany;5. Department of Medicine I, Goethe-University, Frankfurt am Main, Germany;6. Department of Radiation Oncology, Technische Universität München, Ismaninger Str. 22, D-81675 Munich, Germany;7. Clinical Cooperation Group (CCG) “Innate Immunity in Tumor Biology”, Helmholtz Zentrum München, German Research Center for Environmental Health Munich, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany;1. Department of Radiology, University of Texas Health Science Center San Antonio, Mail Code 7800, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA;2. Department of Otolaryngology—Head and Neck Surgery, University of Texas Health Science Center San Antonio, Mail Code 7777, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA;3. Cancer Therapy and Research Center, Mail Code 8232, 7979 Wurzbach Road, San Antonio, TX 78229, USA;1. College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China;2. State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai, People’s Republic of China;1. Radiotherapy Department, Lucien Neuwirth Cancer Institute, St Priest en Jarez, France;2. Radiobiology Laboratory, Lyon Medicine University, Lyon, France;3. Hospices-Civils-de-Lyon, Lyon Hospital, Lyon, France;4. Radiotherapy Department, Gustave Roussy Campus Cancer, Grand Paris, France;5. INSERM 1030, Molecular Radiotherapy, Gustave Roussy Campus Cancer, Grand Paris, France;6. Biological Effects of Radiations, Institut de Recherche Biomédicale des Armées, Brétigny sur Orge, France |
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| Abstract: | Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies. The aggressive behavior of ATC and its resistance to traditional treatment limit the efficacy of radiotherapy, chemotherapy, and surgery. The purpose of this study is aimed at enhancing the therapeutic efficacy of radiotherapy (RT) combined with photothermal therapy (PTT) in murine orthotopic model of ATC, based on our developed single radioactive copper sulfide (CuS) nanoparticle platform. We prepare a new dual-modality therapy for ATC consisting of a single-compartment nanoplatform, polyethylene glycol-coated [64Cu]CuS NPs, in which the radiotherapeutic property of 64Cu is combined with the plasmonic properties of CuS NPs. Mice with Hth83 ATC were treated with PEG-[64Cu]CuS NPs and/or near infrared laser. Antitumor effects were assessed by tumor growth and animal survival. We found that in mice bearing orthotopic human Hth83 ATC tumors, micro-PET/CT imaging and biodistribution studies showed that about 50% of the injected dose of PEG-[64Cu]CuS NPs was retained in tumor 48 h after intratumoral injection. Human absorbed doses were calculated from biodistribution data. In antitumor experiments, tumor growth was delayed by PEG-[64Cu]CuS NP-mediated RT, PTT, and combined RT/PTT, with combined RT/PTT being most effective. In addition, combined RT/PTT significantly prolonged the survival of Hth83 tumor-bearing mice compared to no treatment, laser treatment alone, or NP treatment alone without producing acute toxic effects. These findings indicate that this single-compartment multifunctional NPs platform merits further development as a novel therapeutic agent for ATC. |
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| Keywords: | Radiotherapy Dosimetry Positron emission tomography Photothermal ablation therapy Copper-64 Anaplastic thyroid cancer |
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