Autologous platelet delivery of siRNAs by autologous plasma protein self-assembled nanoparticles for the treatment of acute kidney injury

Abstract Acute kidney injury (AKI) involves the activation of intrarenal hemostatic and inflammatory pathways. Platelets rapidly migrate to affected sites of AKI and release extracellular vesicles (EVs) laden with bioactive mediators that regulate inflammation and hemostasis. While small interfering...

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Main Authors: Jiafan Wang, Hai Huang, Meng Jia, Si Chen, Fengjuan Wang, Guiyang He, Chong Wu, Kaibin Lou, Xuexue Zheng, Heng Zhang, Chao Qin, Yanggang Yuan, Ke Zen, Hongwei Liang
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-025-03338-6
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author Jiafan Wang
Hai Huang
Meng Jia
Si Chen
Fengjuan Wang
Guiyang He
Chong Wu
Kaibin Lou
Xuexue Zheng
Heng Zhang
Chao Qin
Yanggang Yuan
Ke Zen
Hongwei Liang
author_facet Jiafan Wang
Hai Huang
Meng Jia
Si Chen
Fengjuan Wang
Guiyang He
Chong Wu
Kaibin Lou
Xuexue Zheng
Heng Zhang
Chao Qin
Yanggang Yuan
Ke Zen
Hongwei Liang
author_sort Jiafan Wang
collection DOAJ
description Abstract Acute kidney injury (AKI) involves the activation of intrarenal hemostatic and inflammatory pathways. Platelets rapidly migrate to affected sites of AKI and release extracellular vesicles (EVs) laden with bioactive mediators that regulate inflammation and hemostasis. While small interfering RNA (siRNA) is a potent gene-silencing tool for biomedical applications, its therapeutic application in vivo remains challenging. We developed an innovative nucleic acid delivery platform by hybridizing synthetic transformation-related protein 53 (p53) siRNA with autologous plasma and incubating the complex with autologous platelets. These engineered platelets selectively delivered p53 siRNA to injured renal tubular cells via EV-mediated cargo release, resulting in targeted p53 suppression in renal cells and subsequent attenuation of AKI progression. This platelet-centric translational strategy demonstrates significant potential for advancing precision therapies in AKI by exploiting endogenous platelet trafficking to deliver therapeutics directly to injury sites.
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issn 1477-3155
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publishDate 2025-03-01
publisher BMC
record_format Article
series Journal of Nanobiotechnology
spelling doaj-art-d8af3e066860402ca825739b5c6ec8e42025-08-20T02:49:16ZengBMCJournal of Nanobiotechnology1477-31552025-03-0123111710.1186/s12951-025-03338-6Autologous platelet delivery of siRNAs by autologous plasma protein self-assembled nanoparticles for the treatment of acute kidney injuryJiafan Wang0Hai Huang1Meng Jia2Si Chen3Fengjuan Wang4Guiyang He5Chong Wu6Kaibin Lou7Xuexue Zheng8Heng Zhang9Chao Qin10Yanggang Yuan11Ke Zen12Hongwei Liang13Department of Emergency, School of Life Science and Technology, Nanjing Drum Tower Hospital, China Pharmaceutical UniversityDepartment of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical UniversityDepartment of Emergency, School of Life Science and Technology, Nanjing Drum Tower Hospital, China Pharmaceutical UniversityDepartment of Nephrology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Emergency, School of Life Science and Technology, Nanjing Drum Tower Hospital, China Pharmaceutical UniversityDepartment of Emergency, School of Life Science and Technology, Nanjing Drum Tower Hospital, China Pharmaceutical UniversityDepartment of Emergency, School of Life Science and Technology, Nanjing Drum Tower Hospital, China Pharmaceutical UniversityDepartment of Emergency, School of Life Science and Technology, Nanjing Drum Tower Hospital, China Pharmaceutical UniversityDepartment of Emergency, School of Life Science and Technology, Nanjing Drum Tower Hospital, China Pharmaceutical UniversityDepartment of Emergency, School of Life Science and Technology, Nanjing Drum Tower Hospital, China Pharmaceutical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Nephrology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Emergency, School of Life Science and Technology, Nanjing Drum Tower Hospital, China Pharmaceutical UniversityDepartment of Emergency, School of Life Science and Technology, Nanjing Drum Tower Hospital, China Pharmaceutical UniversityAbstract Acute kidney injury (AKI) involves the activation of intrarenal hemostatic and inflammatory pathways. Platelets rapidly migrate to affected sites of AKI and release extracellular vesicles (EVs) laden with bioactive mediators that regulate inflammation and hemostasis. While small interfering RNA (siRNA) is a potent gene-silencing tool for biomedical applications, its therapeutic application in vivo remains challenging. We developed an innovative nucleic acid delivery platform by hybridizing synthetic transformation-related protein 53 (p53) siRNA with autologous plasma and incubating the complex with autologous platelets. These engineered platelets selectively delivered p53 siRNA to injured renal tubular cells via EV-mediated cargo release, resulting in targeted p53 suppression in renal cells and subsequent attenuation of AKI progression. This platelet-centric translational strategy demonstrates significant potential for advancing precision therapies in AKI by exploiting endogenous platelet trafficking to deliver therapeutics directly to injury sites.https://doi.org/10.1186/s12951-025-03338-6Acute kidney injuryPlateletsSelf-assembling nanoparticlesTransformation-related protein 53
spellingShingle Jiafan Wang
Hai Huang
Meng Jia
Si Chen
Fengjuan Wang
Guiyang He
Chong Wu
Kaibin Lou
Xuexue Zheng
Heng Zhang
Chao Qin
Yanggang Yuan
Ke Zen
Hongwei Liang
Autologous platelet delivery of siRNAs by autologous plasma protein self-assembled nanoparticles for the treatment of acute kidney injury
Journal of Nanobiotechnology
Acute kidney injury
Platelets
Self-assembling nanoparticles
Transformation-related protein 53
title Autologous platelet delivery of siRNAs by autologous plasma protein self-assembled nanoparticles for the treatment of acute kidney injury
title_full Autologous platelet delivery of siRNAs by autologous plasma protein self-assembled nanoparticles for the treatment of acute kidney injury
title_fullStr Autologous platelet delivery of siRNAs by autologous plasma protein self-assembled nanoparticles for the treatment of acute kidney injury
title_full_unstemmed Autologous platelet delivery of siRNAs by autologous plasma protein self-assembled nanoparticles for the treatment of acute kidney injury
title_short Autologous platelet delivery of siRNAs by autologous plasma protein self-assembled nanoparticles for the treatment of acute kidney injury
title_sort autologous platelet delivery of sirnas by autologous plasma protein self assembled nanoparticles for the treatment of acute kidney injury
topic Acute kidney injury
Platelets
Self-assembling nanoparticles
Transformation-related protein 53
url https://doi.org/10.1186/s12951-025-03338-6
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