Abstract: TH-PO0030
Mesoscale Nanoparticle-Targeted Therapies to Treat Glomerular Diseases
Session Information
- Bioengineering: MPS, Flow, and Delivery
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bioengineering
- 400 Bioengineering
Authors
- Ghosh, Pratyusha, The City College of New York The Grove School of Engineering, New York, New York, United States
- Vasylaki, Anastasiia, The City College of New York The Grove School of Engineering, New York, New York, United States
- Baltaci, Melis, The City College of New York The Grove School of Engineering, New York, New York, United States
- Roach, Arantxa, The City College of New York The Grove School of Engineering, New York, New York, United States
- Morris, Julia J, The City College of New York The Grove School of Engineering, New York, New York, United States
- Jaimes, Edgar A., Memorial Sloan Kettering Cancer Center, New York, New York, United States
- Wong, Jenny, Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States
- Campbell, Kirk N., University of Pennsylvania Department of Medicine, Philadelphia, Pennsylvania, United States
- Williams, Ryan, Stony Brook University Renaissance School of Medicine, Stony Brook, New York, United States
Background
Proteinuric glomerular diseases are a major cause of chronic kidney disease. We previously showed that polymeric mesoscale nanoparticles (MNPs,300–500 nm),selectively target the kidneys up to 26-fold more than any other organs,are safe,and provide sustained drug release.While MNPs predominantly localize to tubular epithelial cells,we recently found that MNPs are endocytosed by podocytes during glomerular injury. Amiloride,an inhibitor of urokinase-type plasminogen activator(uPA) has antiproteinuric and podocyte protective effects.This study aims to develop siRNA and amiloride-loaded MNPs to treat glomerular injury.
Methods
Mesoscale nanoparticles (MNPs) were synthesized as previously described with a fluorescent Cy5 dye,the FDA-approved diuretic amiloride, and siRNA against the following:TGFβ,ETS-1,and NOX1.MNPs were characterized for size,charge,and loading efficiency.Glomerular disease was induced in mice using lipopolysaccharide(LPS) and in Dahl Salt-Sensitive(DSS) rats with a 4% salt diet.Cy5-MNPs assessed biodistribution and podocyte targeting,while siRNA- and amiloride-loaded MNPs were tested in healthy and diseased animals for therapeutic efficacy.Outcomes measured were proteinuria, renal function, and fibrosis.Organs were imaged post-sacrifice to quantify fluorescence,and immunofluorescence and immunohistochemistry to confirm nanoparticle localization and therapeutic effects.
Results
Dye,siRNA,and amiloride-loaded MNPs were successfully formulated within the 300–450 nm size range and exhibited a ~ –20 mV charge.We found that MNPs loaded with Cy5 fluorescent dye showed accumulation in the kidneys of both healthy and diseased mice,with substantially podocyte accumulation in the kidneys of diseased mice.We found that therapeutic cargo-loaded MNPs demonstrated significant therapeutic efficacy in both disease models,reducing albuminuria/proteinuria and fibrosis,while improving kidney function biomarkers.
Conclusion
We found that kidney-targeting polymeric mesoscale nanoparticles are a potential therapeutic cargo carrier for glomerular kidney diseases,as they demonstrate kidney localization and enhanced podocyte uptake in the context of glomerular disease.We also found that therapeutic cargo-loaded MNPs have the potential to improve kidney function and reduce the long-term effects of renal fibrosis.
Funding
- Other NIH Support