Inulin-based nanoparticles for targeted siRNA delivery in acute kidney injury
Chinmay M Jogdeo1, Sudipta Panja1, Neha Kumari1
1Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Summary
A novel Inulin-CPTA polymer targets injured kidneys, delivering siRNA to silence p53 and improve acute kidney injury (AKI) outcomes in mice. This targeted RNA delivery reduces renal injury and enhances kidney function.
Area of Science:
- Biomaterials Science
- Nanomedicine
- Renal Physiology
Background:
- RNA interference (RNAi) shows therapeutic promise for acute kidney injury (AKI).
- Effective delivery of RNA therapeutics to the kidneys remains a challenge.
- Inulin, a polysaccharide, is explored for its renal targeting potential.
Purpose of the Study:
- To develop a novel renal-targeted polymer for selective siRNA delivery to injured kidneys in AKI.
- To investigate the therapeutic efficacy of p53-targeting siRNA delivered via the novel polymer in a preclinical AKI model.
Main Methods:
- Synthesis of Inulin-CPTA (IC) polymer by conjugating α-cyclam-p-toluic acid (CPTA) to inulin.
- Formation of IC/siRNA nanoparticles (polyplexes) for targeted delivery.
- Evaluation of nanoparticle accumulation, cellular uptake, and p53 silencing in cisplatin-induced AKI mice.
- Assessment of therapeutic outcomes including renal function, injury markers, and inflammation.
Main Results:
- Inulin-CPTA nanoparticles selectively accumulated in injured kidneys, targeting CXCR4-overexpressing cells.
- IC/siRNA polyplexes demonstrated efficient uptake and prolonged retention in injured renal tubules.
- Systemic administration of IC/p53 siRNA nanoparticles potently silenced p53 expression in AKI kidneys.
- Selective p53 knockdown significantly reduced tubular cell death, inflammation, and improved renal function in mice.
Conclusions:
- Inulin-CPTA is a promising biodegradable carrier for renal-targeted delivery of siRNA therapeutics.
- This targeted RNA delivery approach offers a potential new strategy for treating acute kidney injury.
- The IC polymer facilitates selective gene silencing in the injured kidney, leading to improved therapeutic outcomes.
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