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四面体 DNA 纳米结构提高了组蛋白 5 对白色念珠菌的转运效率和抗真菌作用。

Tetrahedral DNA nanostructure improves transport efficiency and anti-fungal effect of histatin 5 against Candida albicans.

机构信息

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

出版信息

Cell Prolif. 2021 May;54(5):e13020. doi: 10.1111/cpr.13020. Epub 2021 Mar 11.

DOI:10.1111/cpr.13020
PMID:33694264
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8088467/
Abstract

OBJECTIVES

Anti-microbial peptides (AMPs) have been comprehensively investigated as a novel alternative to traditional antibiotics against microorganisms. Meanwhile, Tetrahedral DNA nanostructures (TDNs) have gained attention in the field of biomedicine for their premium biological effects and transportation efficiency as delivery vehicles. Hence, in this study, TDN/Histatin 5 (His-5) was synthesized and the transport efficiency and anti-fungal effect were measured to evaluate the promotion of His-5 modified by TDNs.

MATERIALS AND METHODS

Tetrahedral DNA nanostructures/His-5 complex was prepared via electrostatic attraction and characterized by transmission electron microscopy (TEM), polyacrylamide gel electrophoresis (PAGE), dynamic light scattering (DLS) and electrophoretic light scattering (ELS). The anti-fungal effect of the TDN/His-5 complex was evaluated by determining the growth curve and colony-forming units of C. albicans. The morphological transformation of C. albicans was observed by light microscope and scanning electron microscope (SEM). Immunofluorescence was performed, and potassium efflux was detected to mechanistically demonstrate the efficacy of TDN/His-5.

RESULTS

The results showed that Histatin 5 modified by TDNs had preferable stability in serum and was effectively transported into C. albicans, leading to the increased formation of intracellular reactive oxygen species, higher potassium efflux and enhanced anti-fungal effect against C. albicans.

CONCLUSIONS

Our study showed that TDN/His-5 was synthesized successfully. And by the modification of TDNs, His-5 showed increased transport efficiency and improved anti-fungal effect.

摘要

目的

抗菌肽 (AMPs) 作为一种新型的替代传统抗生素的药物，已经在对抗微生物方面得到了广泛的研究。与此同时，四面体 DNA 纳米结构 (TDN) 因其作为递送载体的卓越生物效应和运输效率，在生物医学领域引起了关注。因此，在本研究中，合成了 TDN/Histatin 5（His-5）复合物，并测量了其运输效率和抗真菌效果，以评估 TDN 修饰的 His-5 的促进作用。

材料和方法

通过静电吸引制备四面体 DNA 纳米结构/His-5 复合物，并通过透射电子显微镜（TEM）、聚丙烯酰胺凝胶电泳（PAGE）、动态光散射（DLS）和电泳光散射（ELS）进行表征。通过测定 C. albicans 的生长曲线和菌落形成单位来评估 TDN/His-5 复合物的抗真菌效果。通过光镜和扫描电子显微镜（SEM）观察 C. albicans 的形态转化。通过免疫荧光和钾离子外流检测来阐明 TDN/His-5 的作用机制。

结果

结果表明，TDN 修饰的 Histatin 5 在血清中具有更好的稳定性，并能有效地转运进入 C. albicans，导致细胞内活性氧的形成增加、钾离子外流增加，并增强了对 C. albicans 的抗真菌作用。

结论

本研究成功合成了 TDN/His-5。通过 TDN 的修饰，His-5 的运输效率提高，抗真菌效果得到改善。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fd3/8088467/427ee7956539/CPR-54-e13020-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fd3/8088467/f60074661f79/CPR-54-e13020-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fd3/8088467/5a671c3b4f50/CPR-54-e13020-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fd3/8088467/ea532dd8fbc0/CPR-54-e13020-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fd3/8088467/4ee0e80d8145/CPR-54-e13020-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fd3/8088467/10889bef74bc/CPR-54-e13020-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fd3/8088467/427ee7956539/CPR-54-e13020-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fd3/8088467/f60074661f79/CPR-54-e13020-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fd3/8088467/5a671c3b4f50/CPR-54-e13020-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fd3/8088467/ea532dd8fbc0/CPR-54-e13020-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fd3/8088467/4ee0e80d8145/CPR-54-e13020-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fd3/8088467/10889bef74bc/CPR-54-e13020-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fd3/8088467/427ee7956539/CPR-54-e13020-g007.jpg

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