Framework Nucleic Acids as Blood-Retinal-Barrier-Penetrable Nanocarrier for Periocular Administration

Designing an ocular drugs delivery system that can permeate the outer blood-retinal barrier (oBRB) is crucial for the microinvasive or noninvasive treatment of ocular fundus diseases. However, due to the lack of a nanocarrier that can maintain structure and composition at the oBRB, only intravitreal...

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Veröffentlicht in:ACS applied materials & interfaces 2023-01, Vol.15 (1), p.541-551
Hauptverfasser: Wang, Ruobing, Liu, Yanhan, Xiao, Wenjuan, Yi, Qiuxue, Jiang, Mengmeng, Guo, Ruiyan, Song, Lu, Li, Min, Li, Fan, Shi, Danli, Zhao, Lingyi, Huang, Weiyi, Zuo, Xiaolei, Mao, Xiuhai
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container_end_page 551
container_issue 1
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container_title ACS applied materials & interfaces
container_volume 15
creator Wang, Ruobing
Liu, Yanhan
Xiao, Wenjuan
Yi, Qiuxue
Jiang, Mengmeng
Guo, Ruiyan
Song, Lu
Li, Min
Li, Fan
Shi, Danli
Zhao, Lingyi
Huang, Weiyi
Zuo, Xiaolei
Mao, Xiuhai
description Designing an ocular drugs delivery system that can permeate the outer blood-retinal barrier (oBRB) is crucial for the microinvasive or noninvasive treatment of ocular fundus diseases. However, due to the lack of a nanocarrier that can maintain structure and composition at the oBRB, only intravitreal injection at the eyeball can deliver therapeutics directly to the ocular fundus via paracellular and intercellular routes, despite the intraocular operations risks. Here, we demonstrated tetrahedral framework nucleic acids (tFNAs) can penetrate the oBRB and deliver therapeutic nucleic acids to the retina of the rat eye in vivo following subconjunctival injection. We also discovered that tFNAs were transported via a paracellular route across the intercellular tight junctions at the oBRB. The histology analysis for ocular layers indicated that individual and aptamer/doxorubicin-loaded tFNAs penetrated all layers of the posterior segment of the eyeball to reach the innermost retina and persisted for over 3 days with minimal systemic biodistribution. We expect that the programmability and penetrability of tFNAs will provide a promising method for drug delivery across oBRB and long-term sustenance at the target site via periocular administration to various tissues.
doi_str_mv 10.1021/acsami.2c18042
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subjects Animals
Biological and Medical Applications of Materials and Interfaces
Blood-Retinal Barrier
Drug Delivery Systems - methods
Nucleic Acids
Rats
Retina
Tissue Distribution
title Framework Nucleic Acids as Blood-Retinal-Barrier-Penetrable Nanocarrier for Periocular Administration
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