间充质干细胞工程化的DNA纳米结构构建及其在小鼠肺组织靶向递送中的应用

doi:10.16352/j.issn.1001-6325.2023.07.1110

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (7): 1110-1116.doi: 10.16352/j.issn.1001-6325.2023.07.1110

间充质干细胞工程化的DNA纳米结构构建及其在小鼠肺组织靶向递送中的应用

李卓婷¹, 尚颖旭², 汪海燕¹, 蒋乔², 丁宝全², 李静^1,*, 赵春华^1,*

1.中国医学科学院基础医学研究所北京协和医学院基础学院组织工程中心,北京 100005;
2.国家纳米科学中心中国科学院纳米科学卓越创新中心中国科学院纳米系统与多级次制造重点实验室,北京 100190

收稿日期:2023-03-21 修回日期:2023-05-23 出版日期:2023-07-05 发布日期:2023-07-05
通讯作者: ^*lijing888@ibms.pumc.edu.cn; zhaochunhua@ibms.pumc.edu.cn
基金资助:
中国医学科学院医学与健康科技创新工程(2022-I2M-1-012); 高等学校学科创新引智计划(B18007)

Mesenchymal stem cell-engineered DNA nanostructures and the application in targeted delivery to the lungs of mice

LI Zhuoting¹, SHANG Yingxu², WANG Haiyan¹, JIANG Qiao², DING Baoquan², LI Jing^1,*, ZHAO Chunhua^1,*

1. Center for Excellence in Tissue Engineering, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005;
2. CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China

Received:2023-03-21 Revised:2023-05-23 Online:2023-07-05 Published:2023-07-05

摘要/Abstract

摘要： 目的将三维管状DNA折纸纳米结构(DONs)修饰于间充质干细胞(MSCs)膜表面得到DONs@MSCs,利用MSCs归巢肺组织的特点实现DONs向小鼠肺组织的靶向递送。方法利用计算机辅助工具进行DNA序列设计,得到三维管状DONs。利用原子力显微镜(AFM)表征DONs形貌,并通过琼脂糖凝胶电泳(AGE)验证功能基团的上载。采用生物正交代谢糖工程在MSCs细胞膜表面修饰荧光标记的DNA单链(ssDNA)。根据碱基互补配对原理,将DONs修饰在MSCs膜表面。利用共聚焦显微镜和流式细胞测量术分别检测单链以及DONs的上载情况,并利用活体成像系统观察DONs在小鼠肺组织中的分布。结果成功组装得到DONs。MSCs膜表面成功修饰单链,并成功杂交DONs得到DONs@MSCs。相比静脉注射DONs,DONs@MSCs在小鼠肺部的富集明显增强。结论 DONs@MSCs能够用于DONs向小鼠肺组织的靶向运输,该方法为DONs后续在肺组织递送药物开发了新的策略。

关键词: 间充质干细胞, DNA折纸纳米结构, 靶向递送

Abstract: Objective Modifying 3D tubular DNA origami nanostructures (DONs) onto the mesenchymal stem cells (MSCs) membrane surface to obtain DONs@MSCs. Utilizing the characteristics of MSCs homing lung tissue to achieve targeted delivery of DONs to the lungs of mice. Methods The computer-aided tools for DNA sequence were used to design and obtain obtain pre-designed DONs. The morphology of assembled DONs was characterized by atomic force microscopy(AFM), and the upload of functional groups was verified by agarose gel electrophoresis (AGE). Fluorescent labeled single-strand DNA(ssDNA) was modified on the surface of MSCs using biological orthometabolic sugar engineering. According to the principle of complementary base pairing, DONs were modified on the MSCs surface. Using confocal microscopy and flow cytometry to detect the ssDNA and DONs, and using in vivo imaging to observe the distribution of DONs in lung tissue. Results DONs had been successfully assembled. MSCs membrane surface was successfully modified with ssDNA, and DONs were successfully hybridized to obtain DONs@MSCs. Compared to DONs, the enrichment of DONs@MSCs in the lungs of mice was significantly enhanced. Conclusions DONs@MSCs can be used for DONs targeted delivery to lung tissue of mice. This method provides a new strategy for drug delivery of DONs in lung tissues.

Key words: mesenchymal stem cells, DNA origami nanostructures, targeted delivery

中图分类号:

R318.08

李卓婷, 尚颖旭, 汪海燕, 蒋乔, 丁宝全, 李静, 赵春华. 间充质干细胞工程化的DNA纳米结构构建及其在小鼠肺组织靶向递送中的应用[J]. 基础医学与临床, 2023, 43(7): 1110-1116.

LI Zhuoting, SHANG Yingxu, WANG Haiyan, JIANG Qiao, DING Baoquan, LI Jing, ZHAO Chunhua. Mesenchymal stem cell-engineered DNA nanostructures and the application in targeted delivery to the lungs of mice[J]. Basic & Clinical Medicine, 2023, 43(7): 1110-1116.

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间充质干细胞工程化的DNA纳米结构构建及其在小鼠肺组织靶向递送中的应用

Mesenchymal stem cell-engineered DNA nanostructures and the application in targeted delivery to the lungs of mice

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