title: Radio-photothermal therapy mediated by a single compartment nanoplatform depletes tumor initiating cells and reduces lung metastasis in the orthotopic 4T1 breast tumor model.
abstract: Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and have demonstrated promising application in the clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([(64)Cu]CuS NPs) could suppress breast tumor metastasis through eradication of TICs. Positron electron tomography (PET) imaging and biodistribution studies showed that more than 90% of [(64)Cu]CuS NPs was retained in subcutaneously grown BT474 breast tumor 24 h after intratumoral (i.t.) injection, indicating the NPs are suitable for the combination therapy. Combined RT/PTT therapy resulted in significant tumor growth delay in the subcutaneous BT474 breast cancer model. Moreover, RT/PTT treatment significantly prolonged the survival of mice bearing orthotopic 4T1 breast tumors compared to no treatment, RT alone, or PTT alone. The RT/PTT combination therapy significantly reduced the number of tumor nodules in the lung and the formation of tumor mammospheres from treated 4T1 tumors. No obvious side effects of the CuS NPs were noted in the treated mice in a pilot toxicity study. Taken together, our data support the feasibility of a therapeutic approach for the suppression of tumor metastasis through localized RT/PTT therapy.
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. cli@mdanderson.org and The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. cli@mdanderson.org.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Tian
authors.affiliation: Department of Nuclear Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. cli@mdanderson.org.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Tan
authors.affiliation: Department of Nanomedicine, The Methodist Hospital System Research Institute, Houston, TX 77030, USA.
authors.forename: Haifa
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Nanomedicine, The Methodist Hospital System Research Institute, Houston, TX 77030, USA.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.affiliation: Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. cli@mdanderson.org.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D003301:Copper Radioisotopes / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000637:transplantation; D010789:Phototherapy / Q000379:methods; D011878:Radiotherapy / Q000379:methods; D013440:Sulfides / Q000737:chemistry / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D003301:Copper Radioisotopes; D013440:Sulfides