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结构可切换适体排列的可重构 DNA 纳米网用于靶向癌症治疗。

Structure-switchable aptamer-arranged reconfigurable DNA nanonetworks for targeted cancer therapy.

机构信息

Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, State Key Laboratory of Photocatalysis on Energy and Environment, National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, College of Chemistry, Fuzhou University, Fuzhou 350108, China.

Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, State Key Laboratory of Photocatalysis on Energy and Environment, National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, College of Chemistry, Fuzhou University, Fuzhou 350108, China.

出版信息

Nanomedicine. 2022 Jul;43:102553. doi: 10.1016/j.nano.2022.102553. Epub 2022 Mar 23.

Abstract

The structural DNA nanotechnology holds great potential application in bioimaging, drug delivery and cancer therapy. Herein, an intelligent aptamer-incorporated DNA nanonetwork (Apt-Nnes) is demonstrated for cancer cell imaging and targeted drug delivery, which essentially is a micron-scale pattern with the thickness of double-stranded monolayer. Cancer cell-surface receptors can make it perform magical transformation into small size of nanosheet intermediates and specifically enter target cells. The binding affinity of Apt-Nnes is increased by 3-fold due to multivalent binding effect of aptamers and it can maintain the structural integrity in fetal bovine serum (FBS) for 8 h. More interestingly, target cancer cells can cause the structural disassembly, and each resulting unit transports 4963 doxorubicin (Dox) into target cells, causing the specific cellular cytotoxicity. The cell surface receptor-mediated disassembly of large size of DNA nanostructures into small size of fractions provides a valuable insight into developing intelligent DNA nanostructure suitable for biomedical applications.

摘要

结构 DNA 纳米技术在生物成像、药物输送和癌症治疗方面具有很大的潜在应用。在此,展示了一种智能适体结合 DNA 纳米网络(Apt-Nnes)用于癌细胞成像和靶向药物输送,它本质上是一种具有双链单层厚度的微米级图案。癌细胞表面受体可以使它神奇地转化为纳米片中间体的小尺寸,并特异性进入靶细胞。由于适体的多价结合效应,Apt-Nnes 的结合亲和力提高了 3 倍,并且可以在胎牛血清(FBS)中保持 8 小时的结构完整性。更有趣的是,靶癌细胞可以导致结构解体,每个生成的单元将 4963 个阿霉素(Dox)输送到靶细胞中,引起特定的细胞毒性。大尺寸 DNA 纳米结构在细胞表面受体介导下解组装成小尺寸的片段,为开发适用于生物医学应用的智能 DNA 纳米结构提供了有价值的见解。

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