PMID- 37264740 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20231026 IS - 1613-6829 (Electronic) IS - 1613-6810 (Linking) VI - 19 IP - 40 DP - 2023 Oct TI - Structural Properties and Surface Modification Decided Pharmacokinetic Behavior and Bio-Distribution of DNA Origami Frameworks in Mice. PG - e2302932 LID - 10.1002/smll.202302932 [doi] AB - This study establishes and validates a series of three dimentional (3D) DNA origami frameworks (DOFs) carrying imaging probes to evaluate their pharmacokinetics and real-time bio-distribution in mice. Three typical DOFs with distinguished structural properties are subjected to mice intravenous injection to systematically investigate their in vivo behaviors. Tracing the radioisotope zirconium-89 ((89) Zr) trapped at the inner space of the frameworks, positron emission tomography (PET) imaging is employed to record the real-time bio-distribution 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-dependent. The 43 nm icosahedra framework among the DOFs perform the best in liver targeting, with the ssDNA extensions enhancing this tendency. The modification of triantennary N-acetylgalactosamine (GalNAc), further improves its uptake in liver cells, especially in hepatocytes over other cell types, discovered by flow cytometry analysis. CI - (c) 2023 Wiley-VCH GmbH. FAU - Liu, Dunfang AU - Liu D AD - 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. AD - Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. FAU - Chen, Xiao AU - Chen X AD - 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. FAU - Jiang, Dawei AU - Jiang D AD - 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. FAU - Wang, Cheng AU - Wang C AD - Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. FAU - Xia, Qian AU - Xia Q AD - 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. AD - Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. FAU - Yang, Yang AU - Yang Y AUID- ORCID: 0000-0002-2630-6062 AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230601 PL - Germany TA - Small JT - Small (Weinheim an der Bergstrasse, Germany) JID - 101235338 RN - 0 (Radiopharmaceuticals) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - C6V6S92N3C (Zirconium) RN - 9007-49-2 (DNA) SB - IM MH - Mice MH - Animals MH - *Radiopharmaceuticals/chemistry MH - *Positron-Emission Tomography/methods MH - Polyethylene Glycols/chemistry MH - Zirconium/chemistry MH - DNA MH - Cell Line, Tumor OTO - NOTNLM OT - DNA origami OT - bio-distribution OT - hepatocyte targeting OT - pharmacokinetics OT - radioactive labeling EDAT- 2023/06/02 06:42 MHDA- 2023/10/23 12:42 CRDT- 2023/06/02 03:50 PHST- 2023/05/08 00:00 [revised] PHST- 2023/04/07 00:00 [received] PHST- 2023/10/23 12:42 [medline] PHST- 2023/06/02 06:42 [pubmed] PHST- 2023/06/02 03:50 [entrez] AID - 10.1002/smll.202302932 [doi] PST - ppublish SO - Small. 2023 Oct;19(40):e2302932. doi: 10.1002/smll.202302932. Epub 2023 Jun 1.