Design of Uracil-Modified DNA Nanotubes for Targeted Drug Release via DNA-Modifying Enzyme Reactions
| العنوان: | Design of Uracil-Modified DNA Nanotubes for Targeted Drug Release via DNA-Modifying Enzyme Reactions |
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| المؤلفون: | Yingnan Deng, Yuanhang Tan, YingWei Zhang, Linghao Zhang, ChunYi Zhang, Yonggang Ke, Xin Su |
| المصدر: | ACS Applied Materials & Interfaces. 14:34470-34479 |
| بيانات النشر: | American Chemical Society (ACS), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Drug Liberation, Mice, Nanotubes, DNA Repair, DNA-(Apurinic or Apyrimidinic Site) Lyase, Animals, Humans, General Materials Science, DNA, Uracil, Uracil-DNA Glycosidase |
| الوصف: | DNA nanostructure-based responsive drug delivery has become an increasingly potent method in cancer therapy. However, a variety of important cancer biomarkers have not been explored in searching of new and efficient targeted delivery systems. Uracil degradation glycosylase and human apurinic/apyrimidinic endonuclease are significantly more active in cancer cells. Here, we developed uracil-modified DNA nanotubes that can deliver drugs to tumor cells through an enzyme-induced disassembly process. Although the reaction of these enzymes on their natural DNA substrates has been established, their reactivity on self-assembled nanostructures of nucleic acids is not well understood. We leveraged molecular dynamic simulation based on coarse-grained model to forecast the enzyme reactivity on different DNA designs. The experimental data are highly consistent with the simulation results. It is the first example of molecule simulation being used to guide the design of enzyme-responsive DNA nano-delivery systems. Importantly, we found that the efficiency of drug release from the nanotubes can be regulated by tuning the positions of uracil modification. The DNA nanotubes equipped with cancer-specific aptamer AS1411 are used to deliver doxorubicin to tumor-bearing mice not only effectively inhibiting tumor growth but also protecting major organs from drug-caused damage. We believe that this work provides new knowledge on and insights into future design of enzyme-responsive DNA-based nanocarriers for drug delivery. |
| تدمد: | 1944-8252 1944-8244 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::55a2efad501bca082e0650c6df316367 https://doi.org/10.1021/acsami.2c09488 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....55a2efad501bca082e0650c6df316367 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 19448252 19448244 |
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