Zhou Min, Chen Yunyun, Adachi Makoto, Wen Xiaoxia, Erwin Bill, Mawlawi Osama, Lai Stephen Y, Li Chun
Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Department of Head and Neck Surgery, and Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Biomaterials. 2015 Jul;57:41-9. doi: 10.1016/j.biomaterials.2015.04.013. Epub 2015 Apr 24.
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 [(64)Cu]CuS NPs, in which the radiotherapeutic property of (64)Cu is combined with the plasmonic properties of CuS NPs. Mice with Hth83 ATC were treated with PEG-[(64)Cu]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-[(64)Cu]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-[(64)Cu]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.
间变性甲状腺癌（ATC）是最具侵袭性的人类恶性肿瘤之一。ATC的侵袭性行为及其对传统治疗的抗性限制了放疗、化疗和手术的疗效。基于我们开发的单放射性硫化铜（CuS）纳米颗粒平台，本研究旨在提高放疗（RT）联合光热疗法（PTT）对ATC小鼠原位模型的治疗效果。我们制备了一种针对ATC的新型双模态疗法，其由单室纳米平台聚乙二醇包被的[(64)Cu]CuS纳米颗粒组成，其中(64)Cu的放射治疗特性与CuS纳米颗粒的等离子体特性相结合。用聚乙二醇-[(64)Cu]CuS纳米颗粒和/或近红外激光治疗患有Hth83 ATC的小鼠。通过肿瘤生长和动物存活评估抗肿瘤效果。我们发现，在携带原位人Hth83 ATC肿瘤的小鼠中，微型PET/CT成像和生物分布研究表明，瘤内注射后48小时，约50%的注射剂量聚乙二醇-[(64)Cu]CuS纳米颗粒保留在肿瘤中。根据生物分布数据计算人体吸收剂量。在抗肿瘤实验中，聚乙二醇-[(64)Cu]CuS纳米颗粒介导的放疗、光热疗法以及联合放疗/光热疗法均延迟了肿瘤生长，联合放疗/光热疗法最为有效。此外，与未治疗、单独激光治疗或单独纳米颗粒治疗相比，联合放疗/光热疗法显著延长了荷Hth83肿瘤小鼠的存活时间，且未产生急性毒性作用。这些发现表明，这种单室多功能纳米颗粒平台作为一种用于ATC的新型治疗剂值得进一步开发。
