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基于碳点驱动的自组装 DNA 纳米球用于通过逻辑电路进行肿瘤 microRNAs 成像。

Self-Assembled DNA Nanospheres Driven by Carbon Dots for MicroRNAs Imaging in Tumor via Logic Circuit.

机构信息

School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, 211166, P. R. China.

Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, 211166, P. R. China.

出版信息

Small. 2024 Jun;20(25):e2310728. doi: 10.1002/smll.202310728. Epub 2024 Jan 17.

Abstract

DNA nanostructures with diverse biological functions have made significant advancements in biomedical applications. However, a universal strategy for the efficient production of DNA nanostructures is still lacking. In this work, a facile and mild method is presented for self-assembling polyethylenimine-modified carbon dots (PEI-CDs) and DNA into nanospheres called CANs at room temperature. This makes CANs universally applicable to multiple biological applications involving various types of DNA. Due to the ultra-small size and strong cationic charge of PEI-CDs, CANs exhibit a dense structure with high loading capacity for encapsulated DNA while providing excellent stability by protecting DNA from enzymatic hydrolysis. Additionally, Mg is incorporated into CANs to form Mg@CANs which enriches the performance of CANs and enables subsequent biological imaging applications by providing exogenous Mg. Especially, a DNAzyme logic gate system that contains AND and OR Mg@CANs is constructed and successfully delivered to tumor cells in vitro and in vivo. They can be specifically activated by endogenic human apurinic/apyrimidinic endonuclease 1 and recognize the expression levels of miRNA-21 and miRNA-155 at tumor sites by logic biocomputing. A versatile pattern for delivery of diverse DNA and flexible logic circuits for multiple miRNAs imaging are developed.

摘要

具有多种生物学功能的 DNA 纳米结构在生物医学应用中取得了重大进展。然而,高效生产 DNA 纳米结构的通用策略仍然缺乏。在这项工作中,提出了一种简便温和的方法,可在室温下将聚乙烯亚胺修饰的碳点(PEI-CDs)和 DNA 自组装成称为 CANs 的纳米球。这使得 CANs 普遍适用于涉及多种类型 DNA 的多种生物学应用。由于 PEI-CDs 的超小尺寸和强正电荷,CANs 表现出高密度结构,具有高负载能力的封装 DNA,同时通过保护 DNA 免受酶解提供出色的稳定性。此外,Mg 被掺入 CANs 中以形成 Mg@CANs,这丰富了 CANs 的性能,并通过提供外源 Mg 实现随后的生物成像应用。特别是,构建了包含 AND 和 OR Mg@CANs 的 DNAzyme 逻辑门系统,并成功地在体外和体内递送到肿瘤细胞。它们可以通过内源性人脱嘌呤/脱嘧啶内切酶 1 特异性激活,并通过逻辑生物计算识别肿瘤部位 miRNA-21 和 miRNA-155 的表达水平。开发了用于递送多种 DNA 的通用模式和用于多个 miRNA 成像的灵活逻辑电路。

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