Citation: Mengmeng Yuan, Xiwen Hu, Na Li, Limin Xu, Mengxi Zhu, Xing Pei, Rui Li, Lu Sun, Yupeng Chen, Fei Yu, Huining He. Kidney targeted delivery of siRNA mediated by peptide-siRNA conjugate for the treatment of acute kidney injury[J]. Chinese Chemical Letters, ;2025, 36(6): 110251. doi: 10.1016/j.cclet.2024.110251 shu

Kidney targeted delivery of siRNA mediated by peptide-siRNA conjugate for the treatment of acute kidney injury

Mengmeng Yuan ^{b, d, 1} ,
Xiwen Hu ^{a, b, 1} ,
Na Li ^{c, 1} ,
Limin Xu ^b ,
Mengxi Zhu ^b ,
Xing Pei ^e ,
Rui Li ^b ,
Lu Sun ^b ,
Yupeng Chen ^c ,
Fei Yu ^b ,
Huining He ^{a, b, *}

a.
International Joint Laboratory of Ocular Diseases, School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin 300070, China
b.
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China
c.
Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin 300070, China
d.
Department of Pharmacy, Affiliated Hospital of Shandong Second Medical University, Weifang 261031, China
e.
Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China

hehuining@tmu.edu.cn

Received Date: 16 May 2024
Revised Date: 11 July 2024
Accepted Date: 15 July 2024
Available Online: 15 July 2024

Figures(5)

Small interfering RNA (siRNA), a promising revolutionary therapy, faces delivery obstacles due to its poor targeting, strong charge negativity and macromolecular nature. Clinical-approved siRNAs can now only be delivered to the liver mediated by the chemically conjugated N-acetylgalactosamine (GalNAc) ligand, the conjugate can be effectively uptaken into cells through interaction with asialoglycoprotein receptor (ASGPR) highly expressed on liver hepatocytes. To further explore an efficient non-hepatic targeted delivery strategy, in this study, we designed a delivery system that chemically conjugated p53 siRNA to renal tubular cell-targeting peptides for targeting the kidney, which was suitable for industrial transformation. Results showed that peptide-siRNA conjugate could specifically enter renal tubular epithelial cells and silence target genes. In cisplatin-induced acute kidney injury (AKI) mice, peptide-siRNA conjugate blocked the p53-mediated apoptotic pathway and alleviated renal damage. The innovative proposed system to conjugate kidney-targeting peptides with siRNA achieved the efficient kidney-targeted delivery of siRNA and provided a prospective choice for treating AKI.
- siRNA delivery,
- Kidney target,
- Targeting peptide,
- Conjugate,
- Acute kidney injury
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