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Polycation-siRNA nanoparticles can disassemble at the kidney glomerular basement membrane
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Polycation-siRNA nanoparticles can disassemble at the kidney glomerular basement membrane
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Journal Article
Polycation-siRNA nanoparticles can disassemble at the kidney glomerular basement membrane
2012
Overview
Despite being engineered to avoid renal clearance, many cationic polymer (polycation)-based siRNA nanoparticles that are used for systemic delivery are rapidly eliminated from the circulation. Here, we show that a component of the renal filtration barrier—the glomerular basement membrane (GBM)—can disassemble cationic cyclodextrin-containing polymer (CDP)-based siRNA nanoparticles and, thereby, facilitate their rapid elimination from circulation. Using confocal and electron microscopies, positron emission tomography, and compartment modeling, we demonstrate that siRNA nanoparticles, but not free siRNA, accumulate and disassemble in the GBM. We also confirm that the siRNA nanoparticles do not disassemble in blood plasma in vitro and in vivo. This clearance mechanism may affect any nanoparticles that assemble primarily by electrostatic interactions between cationic delivery components and anionic nucleic acids (or other therapeutic entities).
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Blood
/ Gels
/ Glomerular Basement Membrane - diagnostic imaging
/ Glomerular Basement Membrane - metabolism
/ Heparitin Sulfate - chemistry
/ Kidney
/ Kidneys
/ Kinetics
/ Mice
/ Nanoparticles - administration & dosage
/ Nanoparticles - ultrastructure
/ Plasmas
/ Polymers
/ Positron emission tomography
/ RNA
/ RNA, Small Interfering - administration & dosage
/ RNA, Small Interfering - metabolism
/ siRNA
