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Three typical DOFs with distinguished structural properties are subjected to mice intravenous injection to systematically investigate their in vivo behaviors. Tracing the radioisotope zirconium\u201089 (<jats:sup>89<\/jats:sup>Zr) trapped at the inner space of the frameworks, positron emission tomography (PET) imaging is employed to record the real\u2010time bio\u2010distribution of the structures and acquire their pharmacokinetic parameters in the major metabolic organs. The 3D DOFs show different behavior compared to previous structures, with lower kidney accumulation and higher liver retention. Modifications to the structures, such as exposed ssDNA or polyethylene glycol (PEG) moieties, impact their behavior, but are structure\u2010dependent. The 43\u00a0nm icosahedra framework among the DOFs perform the best in liver targeting, with the ssDNA extensions enhancing this tendency. The modification of triantennary <jats:italic>N<\/jats:italic>\u2010acetylgalactosamine (GalNAc), further improves its uptake in liver cells, especially in hepatocytes over other cell types, discovered by flow cytometry analysis.<\/jats:p>","DOI":"10.1002\/smll.202302932","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T12:36:47Z","timestamp":1685709407000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Structural Properties and Surface Modification Decided Pharmacokinetic Behavior and Bio\u2010Distribution of DNA Origami Frameworks in Mice"],"prefix":"10.1002","volume":"19","author":[{"given":"Dunfang","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Molecular Medicine and Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine State Key Laboratory of Oncogenes and Related Genes Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"},{"name":"Department of Nuclear Medicine Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine and Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine State Key Laboratory of Oncogenes and Related Genes Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology and Hubei Key Laboratory of Molecular Imaging  Wuhan 430022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Xia","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine and Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine State Key Laboratory of Oncogenes and Related Genes Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"},{"name":"Department of Nuclear Medicine Renji Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200127 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2630-6062","authenticated-orcid":false,"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine and Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine State Key Laboratory of Oncogenes and Related Genes Renji Hospital 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