NERDG 2026
Poster 32 Abstract
Targeted Polymer Mesoscale Nanoparticle Therapies for Glomerular Disease
Pratyusha Ghosh (1), Anastasiia Vasylaki (1), Arantxa Roach (1), Melis Baltaci (1,2) , Julia Morris (1) , Edgar A. Jaimes (2), Jenny Wong (3), Kirk Campbell (4), Ryan M. Williams (1,5)
(1) The City College of New York Department of Biomedical Engineering, New York, NY 10031 (2) Memorial Sloan Kettering Cancer Center, New York, NY 10028 (3) Icahn School of Medicine at Mount Sinai, Division of Nephrology, Department of Medicine, New York, NY 10029 (4) University of Pennsylvania, Division of Renal Electrolyte and Hypertension, Department of Medicine, Philadelphia, PA 19104 (5) Stony Brook University, Division of Nephrology and Hypertension, Department of Medicine, Stony Brook, NY 11794
Presenting Author: Pratyusha Ghosh
Corresponding Author: Ryan M. Williams, [email protected]
Purpose
Glomerular disease is a major contributor to end-stage kidney disease. We have previously shown that polymeric mesoscale nanoparticles (MNPs; 300–500 nm) selectively accumulate in the kidney—up to 26-fold more than any other organ—are safe and provide sustained therapeutic release. Although our earlier studies demonstrated preferential localization to tubular epithelial cells, we recently identified podocyte uptake of MNPs during glomerular injury. The purpose of this study is to leverage these findings to develop siRNA- and amiloride-loaded MNPs as targeted therapeutic strategies for glomerular injury.
Methods
Mesoscale nanoparticles (MNPs) were synthesized using established protocols and incorporated a Cy5 fluorescent tracer, siRNA targeting key inflammatory cytokines, or the FDA-approved drug amiloride. The resulting formulations were assessed for physicochemical properties, including particle size, surface charge, and cargo-loading efficiency. Glomerular injury was induced using lipopolysaccharide (LPS) in mice and a 4% high-salt diet in Dahl Salt-Sensitive (DSS) rats. Cy5-labeled MNPs were administered to evaluate whole-body biodistribution and podocyte uptake, whereas therapeutic MNPs containing siRNA or amiloride were tested in both healthy and diseased animals. Experimental endpoints included proteinuria, renal function parameters, and tissue fibrosis. Following sacrifice, major organs were collected for fluorescence quantification, and kidney sections were analyzed via immunofluorescence and immunohistochemistry to verify nanoparticle localization and assess therapeutic effects.
Results
Cy5-, siRNA-, and amiloride-loaded MNPs were successfully generated, exhibiting particle diameters of 300–450 nm and an average surface charge of approximately –20 mV. Cy5-labeled MNPs showed marked kidney enrichment in both healthy and disease groups, with notably increased podocyte uptake in animals with glomerular injury. In both the LPS mouse and DSS rat models, therapeutic MNP formulations produced robust improvements—significantly lowering proteinuria, decreasing renal fibrosis, and enhancing conventional markers of kidney function.
Conclusion
These findings demonstrate that kidney-selective polymeric mesoscale nanoparticles represent a promising platform for delivering therapeutic agents in glomerular disease, marked by strong renal accumulation and increased podocyte uptake during injury. Moreover, MNPs carrying therapeutic cargo improved kidney function and attenuated fibrosis, highlighting their potential to mitigate both acute and long-term consequences of glomerular injury.
Keywords
Glomerular disease, podocyte, polymer mesoscale nanoparticles, siRNA, amiloride, proteinuria
Poster 32 Abstract
Targeted Polymer Mesoscale Nanoparticle Therapies for Glomerular Disease
Pratyusha Ghosh (1), Anastasiia Vasylaki (1), Arantxa Roach (1), Melis Baltaci (1,2) , Julia Morris (1) , Edgar A. Jaimes (2), Jenny Wong (3), Kirk Campbell (4), Ryan M. Williams (1,5)
(1) The City College of New York Department of Biomedical Engineering, New York, NY 10031 (2) Memorial Sloan Kettering Cancer Center, New York, NY 10028 (3) Icahn School of Medicine at Mount Sinai, Division of Nephrology, Department of Medicine, New York, NY 10029 (4) University of Pennsylvania, Division of Renal Electrolyte and Hypertension, Department of Medicine, Philadelphia, PA 19104 (5) Stony Brook University, Division of Nephrology and Hypertension, Department of Medicine, Stony Brook, NY 11794
Presenting Author: Pratyusha Ghosh
Corresponding Author: Ryan M. Williams, [email protected]
Purpose
Glomerular disease is a major contributor to end-stage kidney disease. We have previously shown that polymeric mesoscale nanoparticles (MNPs; 300–500 nm) selectively accumulate in the kidney—up to 26-fold more than any other organ—are safe and provide sustained therapeutic release. Although our earlier studies demonstrated preferential localization to tubular epithelial cells, we recently identified podocyte uptake of MNPs during glomerular injury. The purpose of this study is to leverage these findings to develop siRNA- and amiloride-loaded MNPs as targeted therapeutic strategies for glomerular injury.
Methods
Mesoscale nanoparticles (MNPs) were synthesized using established protocols and incorporated a Cy5 fluorescent tracer, siRNA targeting key inflammatory cytokines, or the FDA-approved drug amiloride. The resulting formulations were assessed for physicochemical properties, including particle size, surface charge, and cargo-loading efficiency. Glomerular injury was induced using lipopolysaccharide (LPS) in mice and a 4% high-salt diet in Dahl Salt-Sensitive (DSS) rats. Cy5-labeled MNPs were administered to evaluate whole-body biodistribution and podocyte uptake, whereas therapeutic MNPs containing siRNA or amiloride were tested in both healthy and diseased animals. Experimental endpoints included proteinuria, renal function parameters, and tissue fibrosis. Following sacrifice, major organs were collected for fluorescence quantification, and kidney sections were analyzed via immunofluorescence and immunohistochemistry to verify nanoparticle localization and assess therapeutic effects.
Results
Cy5-, siRNA-, and amiloride-loaded MNPs were successfully generated, exhibiting particle diameters of 300–450 nm and an average surface charge of approximately –20 mV. Cy5-labeled MNPs showed marked kidney enrichment in both healthy and disease groups, with notably increased podocyte uptake in animals with glomerular injury. In both the LPS mouse and DSS rat models, therapeutic MNP formulations produced robust improvements—significantly lowering proteinuria, decreasing renal fibrosis, and enhancing conventional markers of kidney function.
Conclusion
These findings demonstrate that kidney-selective polymeric mesoscale nanoparticles represent a promising platform for delivering therapeutic agents in glomerular disease, marked by strong renal accumulation and increased podocyte uptake during injury. Moreover, MNPs carrying therapeutic cargo improved kidney function and attenuated fibrosis, highlighting their potential to mitigate both acute and long-term consequences of glomerular injury.
Keywords
Glomerular disease, podocyte, polymer mesoscale nanoparticles, siRNA, amiloride, proteinuria
