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.
Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Small. 2023 Oct;19(40):e2302932. doi: 10.1002/smll.202302932. Epub 2023 Jun 1.
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 ( 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.
本研究建立并验证了一系列携带成像探针的三维（3D）DNA 折纸框架（DOF），以评估它们在小鼠体内的药代动力学和实时生物分布。三种具有不同结构特征的典型 DOF 被用于小鼠静脉注射，以系统地研究它们的体内行为。通过追踪框架内部空间捕获的放射性同位素锆-89（Zr），正电子发射断层扫描（PET）成像被用于记录结构的实时生物分布，并获得它们在主要代谢器官中的药代动力学参数。与之前的结构相比，3D DOF 表现出不同的行为，肾脏的积累较低，肝脏的保留较高。对结构的修饰，如暴露的单链 DNA 或聚乙二醇（PEG）部分，会影响它们的行为，但这种影响是结构依赖性的。DOF 中的 43nm 二十面体框架在肝脏靶向方面表现最佳，ssDNA 延伸增强了这种趋势。通过流式细胞术分析发现，三臂 N-乙酰半乳糖胺（GalNAc）的修饰进一步提高了其在肝细胞中的摄取，特别是在肝细胞中，而在其他细胞类型中则较低。
