ArticleThe Journal of pharmacology and experimental therapeutics2021
Kidney-Targeted Delivery of Prolyl Hydroxylase Domain Protein 2 Small Interfering RNA with Nanoparticles Alleviated Renal Ischemia/Reperfusion Injury.
Article in The Journal of pharmacology and experimental therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Design of Nanocarriers for Kidney Targeted Delivery of Nucleic Acid Therapeutics.Macromolecular bioscience · 2026Review
- Engineering Kidney-Targeted Drug Delivery Systems: Principles, Materials, and Emerging Strategies.International journal of nanomedicine · 2026Review
- RNA-based therapeutic opportunities for the treatment of kidney diseases.Nature reviews. Nephrology · 2026Review
- Scalable Fabrication of High-Payload Dendrimer-Based Nanoparticles for Targeted Atherosclerosis Therapy.ACS applied materials & interfaces · 2025Article
- Autologous platelet delivery of siRNAs by autologous plasma protein self-assembled nanoparticles for the treatment of acute kidney injury.Journal of nanobiotechnology · 2025Article
- Nanotherapeutics in Kidney Disease: Innovations, Challenges, and Future Directions.Journal of the American Society of Nephrology : JASN · 2025Review
- Mitigation of cisplatin-induced acute kidney injury through oral administration of fatty acid amide hydrolase inhibitor PF-04457845.The Journal of pharmacology and experimental therapeutics · 2025Article
- siRNA-mediated therapeutic approaches improve acute kidney injury and limit its worsening.Frontiers in pharmacology · 2025Review
- Nanotechnology-Based Drug Delivery Systems for Treating Acute Kidney Injury.ACS biomaterials science & engineering · 2024Review
- Physiological principles underlying the kidney targeting of renal nanomedicines.Nature reviews. Nephrology · 2024Review
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Genetic Knockout of Fatty Acid Amide Hydrolase Ameliorates Cisplatin-Induced Nephropathy in Mice.Molecular pharmacology · 2023Article
- Using RNA-based therapies to target the kidney in cardiovascular disease.Frontiers in cardiovascular medicine · 2023Review
- Inactivation of fatty acid amide hydrolase protects against ischemic reperfusion injury-induced renal fibrogenesis.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- Liposomal PHD2 Inhibitors and the Enhanced Efficacy in Stabilizing HIF-1α.Nanomaterials (Basel, Switzerland) · 2022Article
- Role of Endothelial Prolyl-4-Hydroxylase Domain Protein/Hypoxia-Inducible Factor Axis in Acute Kidney Injury.Nephron · 2022Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Inhibition of hypoxia-inducible factor-prolyl hydroxylase (PHD) has been shown to protect against various kidney diseases. However, there are controversial reports on the effect of PHD inhibition in renoprotection. The present study determined whether delivery of PHD2 small interfering RNA (siRNA) using an siRNA carrier, folic acid (FA)-decorated polyamidoamine dendrimer generation 5 (G5-FA), would mainly target kidneys and protect against renal ischemia/reperfusion injury (I/R). The renal I/R was generated by clipping the renal pedicle for 30 minutes in uninephrectomized mice. Mice were sacrificed 48 hours after I/R. Normal saline or G5-FA complexed with control or PHD2 siRNA was injected via tail vein 24 hours before ischemia. After the injection of near-infrared fluorescent dye-labeled G5-FA, the fluorescence was mainly detected in kidneys but not in other organs. The reduction of PHD2 mRNA and protein was only observed in kidneys but not in other organs after injection of PHD2-siRNA-G5-FA complex. The injection of PHD2-siRNA-G5-FA significantly alleviated renal I/R injury, as shown by the inhibition of increases in serum creatinine and blood urea nitrogen, the blockade of increases in kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, and the improvement of histologic damage compared with mice treated with control siRNA. PHD2 siRNA can be delivered specifically into kidneys using G5-FA, and that local knockdown of PHD2 gene expression within the kidney alleviates renal I/R injury. Therefore, G5-FA is an efficient siRNA carrier to deliver siRNA into the kidney, and that local inhibition of PHD2 within the kidney may be a potential strategy for the management of acute I/R injury. SIGNIFICANCE STATEMENT: Folic acid (FA)-decorated polyamidoamine dendrimer generation 5 (G5-FA) was demonstrated to be an effective carrier to deliver small interfering RNA (siRNA) into kidneys. Delivery of prolyl hydroxylase domain protein 2 siRNA with G5-FA effectively protected the kidneys against the acute renal ischemia/reperfusion injury.
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