title: ⁶⁴Cu-Doped PdCu@Au Tripods: A Multifunctional Nanomaterial for Positron Emission Tomography and Image-Guided Photothermal Cancer Treatment.
abstract: This article reports a facile synthesis of radiolabeled PdCu@Au core-shell tripods for use in positron emission tomography (PET) and image-guided photothermal cancer treatment by directly incorporating radioactive (64)Cu atoms into the crystal lattice. The tripod had a unique morphology determined by the PdCu tripod that served as a template for the coating of Au shell, in addition to well-controlled specific activity and physical dimensions. The Au shell provided the nanostructure with strong absorption in the near-infrared region and effectively prevented the Cu and (64)Cu atoms in the core from oxidization and dissolution. When conjugated with D-Ala1-peptide T-amide (DAPTA), the core-shell tripods showed great enhancement in targeting the C-C chemokine receptor 5 (CCR5), a newly identified theranostic target up-regulated in triple negative breast cancer (TNBC). Specifically, the CCR5-targeted tripods with an arm length of about 45 nm showed 2- and 6-fold increase in tumor-to-blood and tumor-to-muscle uptake ratios, respectively, relative to their nontargeted counterpart in an orthotopic mouse 4T1 TNBC model at 24 h postinjection. The targeting specificity was further validated via a competitive receptor blocking study. We also demonstrated the use of these targeted, radioactive tripods for effective photothermal treatment in the 4T1 tumor model as guided by PET imaging. The efficacy of treatment was confirmed by the significant reduction in tumor metabolic activity revealed through the use of (18)F-fluorodeoxyglucose PET/CT imaging. Taken together, we believe that the (64)Cu-doped PdCu@Au tripods could serve as a multifunctional platform for both PET imaging and image-guided photothermal cancer therapy.
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University , Atlanta, Georgia 30332, United States.|Department of Biomedical Engineering, College of Engineering, Peking University , Beijing 100871, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Pang
authors.affiliation: Department of Radiology, Washington University School of Medicine , St. Louis, Missouri 63110, United States.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Radiology, Washington University School of Medicine , St. Louis, Missouri 63110, United States.
authors.forename: Hannah
authors.initials: H
authors.lastname: Luehmann
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University , Atlanta, Georgia 30332, United States.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Radiology, Washington University School of Medicine , St. Louis, Missouri 63110, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Detering
authors.affiliation: Department of Radiology, Washington University School of Medicine , St. Louis, Missouri 63110, United States.
authors.forename: Meng
authors.initials: M
authors.lastname: You
authors.affiliation: Laboratory of Optical Physics, Institute of Physics, Chinese Academy of Sciences , Beijing 100190, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University , Atlanta, Georgia 30332, United States.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Laboratory of Optical Physics, Institute of Physics, Chinese Academy of Sciences , Beijing 100190, P. R. China.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, College of Engineering, Peking University , Beijing 100871, P. R. China.
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Ren
authors.affiliation: Department of Radiology, Washington University School of Medicine , St. Louis, Missouri 63110, United States.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University , Atlanta, Georgia 30332, United States.
authors.forename: Younan
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006046:Gold / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006979:Hyperthermia, Induced / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000737:chemistry* / Q000627:therapeutic use; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010165:Palladium / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010789:Phototherapy / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods; D019713:Receptors, CCR5 / Q000032:analysis / Q000378:metabolism; D000068936:Theranostic Nanomedicine
chemical_list: D019713:Receptors, CCR5; D010165:Palladium; D006046:Gold; D003300:Copper
keywords: CCR5 targeting; breast cancer; core−shell tripod; photothermal treatment; radiolabeling