Single agent nanoparticle for radiotherapy and radio-photothermal therapy in anaplastic thyroid cancer.
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.
Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Min
M
Zhou
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.
Yunyun
Y
Chen
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.
Makoto
M
Adachi
Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Xiaoxia
X
Wen
Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Bill
B
Erwin
Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Osama
O
Mawlawi
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. Electronic address: sylai@mdanderson.org.
Stephen Y
SY
Lai
Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. Electronic address: cli@mdanderson.org.
Chun
C
Li
D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods; D003300:Copper / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003301:Copper Radioisotopes / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D053685:Laser Therapy / Q000379:methods; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use* / Q000648:ultrastructure; D010789:Phototherapy / Q000379:methods; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D013440:Sulfides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D065646:Thyroid Carcinoma, Anaplastic / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D013961:Thyroid Gland / Q000473:pathology / Q000528:radiation effects; D013964:Thyroid Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*
D003301:Copper Radioisotopes; D013440:Sulfides; C099343:cuprous sulfide; D011092:Polyethylene Glycols; D003300:Copper
Anaplastic thyroid cancer; Copper-64; Dosimetry; Photothermal ablation therapy; Positron emission tomography; Radiotherapy