Targeting kidney mesangium by nanoparticles of defined size

Abstract

Nanoparticles are being investigated for numerous medical applications and are showing potential as an emerging class of carriers for drug delivery. Investigations on how the physicochemical properties (e.g., size, surface charge, shape, and density of targeting ligands) of nanoparticles enable their ability to overcome biological barriers and reach designated cellular destinations in sufficient amounts to elicit biological efficacy are of interest. Despite proven success in nanoparticle accumulation at cellular locations and occurrence of downstream therapeutic effects (e.g., target gene inhibition) in a selected few organs such as tumor and liver, reports on effective delivery of engineered nanoparticles to other organs still remain scarce. Here, we show that nanoparticles of ∼75 ± 25-nm diameters target the mesangium of the kidney. These data show the effects of particle diameter on targeting the mesangium of the kidney. Because many diseases originate from this area of the kidney, our findings establish design criteria for constructing nanoparticle-based therapeutics for targeting diseases that involve the mesangium of the kidney.gold nanoparticles | kidney targeting | mesangial cells | particle size

Polycation-siRNA nanoparticles can disassemble at the kidney glomerular basement membrane

“…These data are consistent with the results from our confocal microscopy study, where we observed some nonglomerular renal vessels with appreciable fluorescence signal in their walls in tissue from mice receiving siRNA nanoparticle treatment. Renal peri-tubule endothelial cell uptake of pegylated gold nanoparticles has been observed (14) and may be a generalized phenomenon for nanoparticle systems.…”

“…Gold nanoparticles of up to 130 nm in size can cross the fenestrated glomerular endothelium but not the GBM (14). Therefore, we believe that siRNA nanoparticles of diameters of ≈100 nm in circulation can access the GBM and preferentially deposit there because of their positive surface charge.…”

“…These three layers are the glomerular endothelial fenestrations (≈100 nm) (14), the glomerular basement membrane (GBM), a 300-nm-thick connective tissue membrane rich in heparan sulfate (15) (pore size of 3 nm) (16) and the podocyte filtration slits (≈32 nm) (17). The renal filtration barrier, in its entirety, possesses an effective size cutoff of ≈10 nm, and is known to facilitate the rapid renal clearance of small molecules drugs and free siRNA.…”

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…Specific targeted delivery of therapeutic agents to kidneys, and even to specific renal cells in the glomeruli or the tubulointerstitium, seems feasible (442)(443)(444)(445)(446)(447) and might open the possibility of using drugs that would otherwise be limited by systemic toxicity. Such approaches may also be combined with contrast agents for non-invasive imaging allowing a ''theranostic'' strategy which is currently mainly being developed for cancer applications.…”

In vitro study of the interaction of heregulin-functionalized magnetic–optical nanorods with MCF7 and MDA-MB-231 cells

“…5,6 Targeting of specific cell types in vivo for diagnostic and therapeutic purposes has remained a challenge due to the 30 numerous macromolecular components of blood that adsorb on nanoparticles and the body's multiple mechanisms for clearing nanoparticles from the circulation. 7,8 Nanoparticle surfaces are typically coated with a polymer monolayer, such as, dextran or polyethyleneglycol (PEG), to improve their stability and biocompatibility, and prolong their blood half-life. These polymer coatings decrease the amount of protein that adsorb on the nanoparticle surface and increase the hydrodynamic size of the particles sparing the smaller particles from rapid elimination in the reticuloendothelial system.…”