Soft Matter · 2009 · 259 citations · 29 references
PharmacyBiomedical EngineeringCell BiologyBiomaterialsDrug DeliveryNanoparticle Drug DeliveryCell-nanoparticle InteractionsCellular UptakeGelsHydrogelsIntracellular Drug DeliveryPolymeric NanoparticlesCellular Trafficking Of NanoparticlesClathrin-mediated EntryHydrogel FormulationsHydrogel NanoparticlesNanogelsNanoparticle Cellular UptakeNanoparticle Intracellular TransportNanoparticles
Uptake and intracellular trafficking of hydrogel nanoparticles (NPs) of N,N-diethyl acrylamide and 2-hydroxyethyl methacrylate crosslinked with N,N′-methylene-bis-acrylamide were studied with a RAW 264.7 murine macrophage cell line. Results show that the uptake rate, the mechanism of internalization and the concentration of internalized NPs are correlated to the NP Young modulus. Soft NPs are found to be internalized preferentially via macropinocytosis while the uptake of stiff NPs is mediated by a clathrin-dependent mechanism. NPs with an intermediate Young modulus exhibit multiple uptake mechanisms. The accumulation rate of the NPs into lysosomal compartments of the cell is also dependent on the NP elasticity. Our results suggest that control over the mechanical properties of hydrogel NPs can be used to tailor the cellular uptake mechanism and kinetics of drug delivery.
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