细胞内
阳离子聚合
生物物理学
DNA
DNA折纸
细胞质
纳米技术
聚合物
材料科学
化学
纳米结构
生物化学
生物
高分子化学
复合材料
作者
Sarah Youssef,Emily Tsang,Anirban Samanta,Vipin Kumar,Kurt V. Gothelf
出处
期刊:Small
[Wiley]
日期:2023-11-02
卷期号:20 (10)
被引量:1
标识
DOI:10.1002/smll.202301058
摘要
DNA nanostructures have considerable biomedical potential as intracellular delivery vehicles as they are highly homogeneous and can be functionalized with high spatial resolution. However, challenges like instability under physiological conditions, limited cellular uptake, and lysosomal degradation limit their use. This paper presents a bio-reducible, cationic polymer poly(cystaminebisacrylamide-1,6-diaminohexane) (PCD) as a reversible DNA origami protector. PCD displays a stronger DNA affinity than other cationic polymers. DNA nanostructures with PCD protection are shielded from low salt conditions and DNase I degradation and show a 40-fold increase in cell-association when linked to targeting antibodies. Confocal microscopy reveals a potential secondary cell uptake mechanism, directly delivering the nanostructures to the cytoplasm. Additionally, PCD can be removed by cleaving its backbone disulfides using the intracellular reductant, glutathione. Finally, the application of these constructs is demonstrated for targeted delivery of a cytotoxic agent to cancer cells, which efficiently decreases their viability. The PCD protective agent that is reported here is a simple and efficient method for the stabilization of DNA origami structures. With the ability to deprotect the DNA nanostructures upon entry of the intracellular space, the possibility for the use of DNA origami in pharmaceutical applications is enhanced.
科研通智能强力驱动
Strongly Powered by AbleSci AI