title: In Vivo Targeting and Positron Emission Tomography Imaging of Tumor with Intrinsically Radioactive Metal-Organic Frameworks Nanomaterials.
abstract: Nanoscale metal-organic frameworks (nMOF) materials represent an attractive tool for various biomedical applications. Due to the chemical versatility, enormous porosity, and tunable degradability of nMOFs, they have been adopted as carriers for delivery of imaging and/or therapeutic cargos. However, the relatively low stability of most nMOFs has limited practical in vivo applications. Here we report the production and characterization of an intrinsically radioactive UiO-66 nMOF (89Zr-UiO-66) with incorporation of positron-emitting isotope zirconium-89 (89Zr).89Zr-UiO-66 was further functionalized with pyrene-derived polyethylene glycol (Py-PGA-PEG) and conjugated with a peptide ligand (F3) to nucleolin for targeting of triple-negative breast tumors. Doxorubicin (DOX) was loaded onto UiO-66 with a relatively high loading capacity (1 mg DOX/mg UiO-66) and served as both a therapeutic cargo and a fluorescence visualizer in this study. Functionalized89Zr-UiO-66 demonstrated strong radiochemical and material stability in different biological media. Based on the findings from cellular targeting and in vivo positron emission tomography (PET) imaging, we can conclude that89Zr-UiO-66/Py-PGA-PEG-F3 can serve as an image-guidable, tumor-selective cargo delivery nanoplatform. In addition, toxicity evaluation confirmed that properly PEGylated UiO-66 did not impose acute or chronic toxicity to the test subjects. With selective targeting of nucleolin on both tumor vasculature and tumor cells, this intrinsically radioactive nMOF can find broad application in cancer theranostics.
authors.affiliation: Department of Radiology, Center for Molecular Imaging, University of Michigan , Ann Arbor, Michigan 48109-2200, United States.
authors.forename: Daiqin
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Radiology, Center for Molecular Imaging, University of Michigan , Ann Arbor, Michigan 48109-2200, United States.|Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University , Xuzhou, Jiangsu 221004, China.
authors.forename: Dongzhi
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Radiology, Center for Molecular Imaging, University of Michigan , Ann Arbor, Michigan 48109-2200, United States.
authors.forename: Casey A
authors.initials: CA
authors.lastname: Dougherty
authors.affiliation: Department of Radiology, Center for Molecular Imaging, University of Michigan , Ann Arbor, Michigan 48109-2200, United States.|College of Animal Sciences and Veterinary Medicine, Henan Agriculture University , Zhengzhou, Henan 450002, China.
authors.forename: Weifei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Radiology, Center for Molecular Imaging, University of Michigan , Ann Arbor, Michigan 48109-2200, United States.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wu
authors.affiliation: Key Laboratory of Optoelectronic Chemical Materials and Devices, Jianghan University , Wuhan, Hubei 430056, China.
authors.forename: Xianran
authors.initials: X
authors.lastname: He
authors.affiliation: School of Pharmacy, China Pharmaceutical University , Nanjing 210009, China.
authors.forename: Ting
authors.identifier: 0000-0001-7510-9295
authors.initials: T
authors.lastname: Cai
authors.affiliation: Department of Radiology, Center for Molecular Imaging, University of Michigan , Ann Arbor, Michigan 48109-2200, United States.|Comprehensive Cancer Center, University of Michigan , Ann Arbor, Michigan 48109-0944, United States.
authors.forename: Marcian E
authors.identifier: 0000-0002-6538-4661
authors.initials: ME
authors.lastname: Van Dort
authors.affiliation: Department of Radiology, Center for Molecular Imaging, University of Michigan , Ann Arbor, Michigan 48109-2200, United States.|Comprehensive Cancer Center, University of Michigan , Ann Arbor, Michigan 48109-0944, United States.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Ross
authors.affiliation: Department of Radiology, Center for Molecular Imaging, University of Michigan , Ann Arbor, Michigan 48109-2200, United States.|Key Laboratory of Optoelectronic Chemical Materials and Devices, Jianghan University , Wuhan, Hubei 430056, China.|Comprehensive Cancer Center, University of Michigan , Ann Arbor, Michigan 48109-0944, United States.
authors.forename: Hao
authors.identifier: 0000-0002-9730-9367
authors.initials: H
authors.lastname: Hong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005260:Female; D006801:Humans; D000073396:Metal-Organic Frameworks / Q000737:chemistry* / Q000633:toxicity; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy*; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D049268:Positron-Emission Tomography; D011868:Radioisotopes / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000737:chemistry*; D014018:Tissue Distribution; D015040:Zirconium / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D004337:Drug Carriers; D000073396:Metal-Organic Frameworks; D010455:Peptides; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D011092:Polyethylene Glycols; D004317:Doxorubicin; D015040:Zirconium; C000615502:Zirconium-89
keywords: cancer targeting; image-guided drug delivery; intrinsic radiolabel; metal−organic frameworks (MOF); nucleolin; positron emission tomography