Jia-Hao Bai, Qing-Tao Yu, Yi-Wu Wang, Chun-Fa Chen, Lian-Ju Ma, Yue Yuan, Yong-Jun Gan, Jia-Qi Yang, Shu Zhu, Yu-Hang Ran, Li-Lei Zhang, Hang Qian, Zheng-Huan Zhao and Qian Liu
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引用次数: 0
摘要
自组装 DNA 纳米结构在生物传感、药物传输和纳米医学领域大有可为。然而,DNA 纳米结构在生理条件下的不稳定性和低细胞吸收效率等挑战限制了其实际应用。为了解决这些障碍,本研究提出了一种将阳离子聚合物聚乙烯亚胺(PEI)与 DNA 自组装相结合的新方法。假设带正电荷的线性聚乙烯亚胺能促进 DNA 纳米结构的自组装,保护它们免受恶劣条件的影响,并赋予它们聚乙烯亚胺的细胞渗透特性。实验证明,通过 PEI 介导成功合成了 DNA 纳米管(PNT),与传统的 Mg2+ 组装 DNA 纳米管相比,PNT 的稳定性和细胞吸收效率显著提高。研究进一步发现,在 PEI 和 DNA 的共同作用下,其内吞机制既有凝集素介导的内吞,也有洞穴素介导的内吞。为了展示这种混合纳米结构在生物医学领域的适用性,装载了 KRAS siRNA 的 PNT 被有效地输送到肺腺癌细胞中,在体外产生了良好的抗癌效果。这些研究结果表明,PEI 介导的 DNA 组装可能成为未来生物医学应用的重要工具。
Polyethyleneimine-mediated assembly of DNA nanotubes for KRAS siRNA delivery in lung adenocarcinoma therapy†
Self-assembled DNA nanostructures hold great promise in biosensing, drug delivery and nanomedicine. Nevertheless, challenges like instability and inefficiency in cellular uptake of DNA nanostructures under physiological conditions limit their practical use. To tackle these obstacles, this study proposes a novel approach that integrates the cationic polymer polyethyleneimine (PEI) with DNA self-assembly. The hypothesis is that the positively charged linear PEI can facilitate the self-assembly of DNA nanostructures, safeguard them against harsh conditions and impart them with the cellular penetration characteristic of PEI. As a demonstration, a DNA nanotube (PNT) was successfully synthesized through PEI mediation, and it exhibited significantly enhanced stability and cellular uptake efficiency compared to conventional Mg2+-assembled DNA nanotubes. The internalization mechanism was further found to be both clathrin-mediated and caveolin-mediated endocytosis, influenced by both PEI and DNA. To showcase the applicability of this hybrid nanostructure for biomedical settings, the KRAS siRNA-loaded PNT was efficiently delivered into lung adenocarcinoma cells, leading to excellent anticancer effects in vitro. These findings suggest that the PEI-mediated DNA assembly could become a valuable tool for future biomedical applications.
期刊介绍:
Journal of Materials Chemistry A, B & C cover high quality studies across all fields of materials chemistry. The journals focus on those theoretical or experimental studies that report new understanding, applications, properties and synthesis of materials. Journal of Materials Chemistry A, B & C are separated by the intended application of the material studied. Broadly, applications in energy and sustainability are of interest to Journal of Materials Chemistry A, applications in biology and medicine are of interest to Journal of Materials Chemistry B, and applications in optical, magnetic and electronic devices are of interest to Journal of Materials Chemistry C.Journal of Materials Chemistry B is a Transformative Journal and Plan S compliant. Example topic areas within the scope of Journal of Materials Chemistry B are listed below. This list is neither exhaustive nor exclusive:
Antifouling coatings
Biocompatible materials
Bioelectronics
Bioimaging
Biomimetics
Biomineralisation
Bionics
Biosensors
Diagnostics
Drug delivery
Gene delivery
Immunobiology
Nanomedicine
Regenerative medicine & Tissue engineering
Scaffolds
Soft robotics
Stem cells
Therapeutic devices