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