Proceedings of the National Academy of Sciences · 2011 · 493 citations · 16 references
PharmacyNephrologyPharmaceuticsDrug DeliveryNanomaterialsNanoparticle Drug DeliveryInorganic NanoparticlesNanocarriers For TherapeuticsNanomaterials For Drug DeliveryNanomedicineNanoparticle CharacterizationNanoparticle DesignDesign CriteriaDrug Distribution Across Biological BarriersNanoparticle AccumulationNanoparticle DeliveryNanoparticle Drug TargetingNanoparticle PharmacologyRenal TargetingTransport Across Biological Barriers
Nanoparticles are being explored as drug carriers, but their size, charge, shape, and ligand density determine their ability to cross biological barriers, and delivery to organs beyond tumors and liver remains limited. We demonstrate that ~75 nm nanoparticles preferentially accumulate in the kidney mesangium, revealing diameter‑dependent targeting that informs design of mesangium‑directed therapeutics.
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.
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