Electrostatic Attractive Self-Delivery of siRNA and Light-Induced Self-Escape for Synergistic Gene Therapy

© 2023 Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 30 vom: 21. Juli, Seite e2301409
1. Verfasser: Yang, Yuxin (VerfasserIn)
Weitere Verfasser: Ning, Haijun, Xia, Tianping, Du, Jianjun, Sun, Wen, Fan, Jiangli, Peng, Xiaojun
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2023
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article gene therapy lysosome escape photodynamic therapy self-delivery siRNA RNA, Small Interfering Photosensitizing Agents
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520 |a Small interfering RNA (siRNA) holds immense promise for suppressing gene expression and treating various life-threatening diseases, including cancer. However, efficient delivery and lysosomal escape remain critical challenges that hinder the therapeutic effectiveness of siRNA. Herein, cationic photosensitizer (NB-Br) is grafted onto polo-like kinase 1 (PLK1) siRNA to form an amphiphilic siRNA-photosensitizer conjugate (siPLK1-NB), which can self-assemble into nanoparticles (siPLK1-NB NPs) via electrostatic attraction. Notably, siPLK1-NB NPs exhibit rapid and efficient cell endocytosis, as well as outstanding tumor-targeting property in multiple tumor-bearing mice models. When siPLK1-NB NPs are located inside tumor cell lysosomes, the generated reactive oxygen species (ROS) after photoactivation can disrupt the lysosome membrane structure and facilitate siRNA escape from lysosomes. Under light irradiation, siPLK1-NB NPs can downregulate PLK1 expression and induce photodynamic killing, effectively inhibiting tumor cell growth both in vitro and in vivo. Consequently, this study provides a novel design strategy for carrier-free siRNA delivery systems. As far as it is known, this is the first report of a carrier-free siRNA delivery system based on electrostatic attraction 
650 4 |a Journal Article 
650 4 |a gene therapy 
650 4 |a lysosome escape 
650 4 |a photodynamic therapy 
650 4 |a self-delivery 
650 4 |a siRNA 
650 7 |a RNA, Small Interfering  |2 NLM 
650 7 |a Photosensitizing Agents  |2 NLM 
700 1 |a Ning, Haijun  |e verfasserin  |4 aut 
700 1 |a Xia, Tianping  |e verfasserin  |4 aut 
700 1 |a Du, Jianjun  |e verfasserin  |4 aut 
700 1 |a Sun, Wen  |e verfasserin  |4 aut 
700 1 |a Fan, Jiangli  |e verfasserin  |4 aut 
700 1 |a Peng, Xiaojun  |e verfasserin  |4 aut 
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773 1 8 |g volume:35  |g year:2023  |g number:30  |g day:21  |g month:07  |g pages:e2301409 
856 4 0 |u http://dx.doi.org/10.1002/adma.202301409  |3 Volltext 
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