中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 合肥物质科学研究院
  3. 中国科学院合肥物质科学研究院
Epigallocatechin gallate-loaded tetrahedral DNA nanostructures as a novel inner ear drug delivery system

文献类型：期刊论文

作者Chen, Yuming2,3,5; Gu, Jiayi2,3,5; Liu, Yan1,6,7; Xu, Ke2,3,5; Song, Jie1,6,7; Wang, Xueling2,3,5; Yu, Dehong2,3,4,5; Wu, Hao2,3,5
刊名NANOSCALE
出版日期2022-06-09
卷号14
ISSN号2040-3364
DOI10.1039/d1nr07921b
通讯作者Wang, Xueling(xuelingwang2013@163.com) ; Yu, Dehong(dehongyu@126.com) ; Wu, Hao(wuhao@shsmu.edu.cn)
英文摘要The study of drug delivery systems to the inner ear is a crucial but challenging field. The sensory organ (in the inner ear) is protected by the petrous bone labyrinth and the membranous labyrinth, both of which need to be overcome during the drug delivery process. The requirements for such a delivery system include small size, appropriate flexibility and biodegradability. DNA nanostructures, biomaterials that can arrange multiple functional components with nanometer precision, exhibit characteristics that are compatible with the requirements for inner ear drug delivery. Herein, we report the development of a novel inner ear drug delivery system based on epigallocatechin gallate (EGCG)-loaded tetrahedral DNA nanostructures (TDNs, EGCG@TDNs). The TDNs self-assembled via base-pairing of four single-stranded DNA constructs and EGCG was loaded into the TDNs through non-covalent interactions. Cy5-labeled TDNs (Cy5-TDNs) were significantly internalized by the House Ear Institute-Organ of Corti 1 cell line, and this endocytosis was energy-, clathrin-, and micropinocytosis-dependent. Cy5-TDNs penetrated the round window membrane (RWM) rapidly in vivo. Local application of EGCG@TDNs onto the RWM of guinea pigs in a single dose continuously released EGCG over 4 hours. Drug concentrations in the perilymph were significantly elevated compared with the administration of free EGCG at the same dose. EGCG@TDNs were found to have favorable biocompatibility and strongly affected the RSL3-induced down-regulation of GPX4 and the generation of reactive oxygen species, on the basis of 2 ',7 '-dichlorodihydrofluorescein diacetate staining. JC-1 staining suggested that EGCG@TDNs successfully reversed the decrease in mitochondrial membrane potential induced by RSL-3 in vitro and rescued cells from apoptosis, as demonstrated by the analysis of Annexin V-FITC/PI staining. Further functional studies showed that a locally administered single-dose of EGCG@TDNs effectively preserved spiral ganglion cells in C57/BL6 mice after noise-induced hearing loss. Hearing loss at 5.6 and 8 kHz frequencies was significantly attenuated when compared with the control EGCG formulation. Histological analyses indicated that the administration of TDNs and EGCG@TDNs did not induce local inflammatory responses. These favorable histological and functional effects resulting from the delivery of EGCG by TDNs through a local intratympanic injection suggest potential for therapeutic benefit in clinical applications.
WOS关键词CURRENT CHALLENGES ; NANOPARTICLES ; MECHANISM ; MEMBRANE ; THERAPY ; COCHLEA ; CELLS ; MODEL
资助项目Natural Science Foundation of Shanghai[19ZR1429400] ; Natural Science Foundation of Shanghai[21ZR1437600] ; National Natural Science Foundation of China[81970874] ; State Key Program of National Natural Science Foundation of China[81330023] ; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases[14DZ2260300] ; Innovative Research Team of High-level Local universities in Shanghai
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种英语
出版者ROYAL SOC CHEMISTRY
WOS记录号WOS:000797625200001
资助机构Natural Science Foundation of Shanghai ; National Natural Science Foundation of China ; State Key Program of National Natural Science Foundation of China ; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases ; Innovative Research Team of High-level Local universities in Shanghai
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/130881]  
专题中国科学院合肥物质科学研究院
通讯作者Wang, Xueling; Yu, Dehong; Wu, Hao
作者单位1.Shanghai Jiao Tong Univ, Sch Elect Informat & Elect Engn, Inst Nano Biomed & Engn, Dept Instrument Sci & Engn, Shanghai 200240, Peoples R China
2.Shanghai Key Lab Translat Med Ear & Nose Dis 14DZ, Shanghai 200011, Peoples R China
3.Shanghai Jiao Tong Univ, Ear Inst, Sch Med, Shanghai 200011, Peoples R China
4.Shanghai Univ, Sch Life Sci, Materdicine Lab, Shanghai 200444, Peoples R China
5.Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Otolaryngol Head & Neck Surg, Sch Med, Shanghai 200011, Peoples R China
6.Univ Chinese Acad Sci, Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China
7.Chinese Acad Sci, Inst Canc & Basic Med ICBM, Hangzhou 310022, Zhejiang, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Yuming,Gu, Jiayi,Liu, Yan,et al. Epigallocatechin gallate-loaded tetrahedral DNA nanostructures as a novel inner ear drug delivery system[J]. NANOSCALE,2022,14.
APA Chen, Yuming.,Gu, Jiayi.,Liu, Yan.,Xu, Ke.,Song, Jie.,...&Wu, Hao.(2022).Epigallocatechin gallate-loaded tetrahedral DNA nanostructures as a novel inner ear drug delivery system.NANOSCALE,14.
MLA Chen, Yuming,et al."Epigallocatechin gallate-loaded tetrahedral DNA nanostructures as a novel inner ear drug delivery system".NANOSCALE 14(2022).

入库方式： OAI收割

来源：合肥物质科学研究院

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。