The effect of particle agglomeration on the formation of a surface-connected compartment induced by hydroxyapatite nanoparticles in human monocyte-derived macrophages

TY - JOUR

T1 - The effect of particle agglomeration on the formation of a surface-connected compartment induced by hydroxyapatite nanoparticles in human monocyte-derived macrophages

AU - Mueller, Karin H.

AU - Motskin, Michael

AU - Philpott, Alistair J.

AU - Routh, Alexander F.

AU - Shanahan, Catherine M.

AU - Duer, Melinda J.

AU - Skepper, Jeremy N.

PY - 2014/1

Y1 - 2014/1

N2 - Agglomeration dramatically affects many aspects of nanoparticle-cell interactions. Here we show that hydroxyapatite nanoparticles formed large agglomerates in biological medium resulting in extensive particle uptake and dose-dependent cytotoxicity in human macrophages. Particle citration and/or the addition of the dispersant Darvan 7 dramatically reduced mean agglomerate sizes, the amount of particle uptake and concomitantly cytotoxicity. More surprisingly, agglomeration governed the mode of particle uptake. Agglomerates were sequestered within an extensive, interconnected membrane labyrinth open to the extracellular space. In spite of not being truly intracellular, imaging studies suggest particle degradation occurred within this surface-connected compartment (SCC). Agglomerate dispersion prevented the SCC from forming, but did not completely inhibit nanoparticle uptake by other mechanisms. The results of this study could be relevant to understanding particle cell interactions during developmental mineral deposition, in ectopic calcification in disease, and during application of hydroxyapatite nanoparticle vectors in biomedicine.

AB - Agglomeration dramatically affects many aspects of nanoparticle-cell interactions. Here we show that hydroxyapatite nanoparticles formed large agglomerates in biological medium resulting in extensive particle uptake and dose-dependent cytotoxicity in human macrophages. Particle citration and/or the addition of the dispersant Darvan 7 dramatically reduced mean agglomerate sizes, the amount of particle uptake and concomitantly cytotoxicity. More surprisingly, agglomeration governed the mode of particle uptake. Agglomerates were sequestered within an extensive, interconnected membrane labyrinth open to the extracellular space. In spite of not being truly intracellular, imaging studies suggest particle degradation occurred within this surface-connected compartment (SCC). Agglomerate dispersion prevented the SCC from forming, but did not completely inhibit nanoparticle uptake by other mechanisms. The results of this study could be relevant to understanding particle cell interactions during developmental mineral deposition, in ectopic calcification in disease, and during application of hydroxyapatite nanoparticle vectors in biomedicine.

KW - Hydroxyapatite nanoparticles

KW - Agglomeration

KW - Aggregation

KW - Cytotoxicity

KW - Macrophages

KW - Surface-connected compartment

KW - AMORPHOUS SILICA NANOPARTICLES

KW - COLLOIDAL STABILITY

KW - IN-VITRO

KW - NALP3 INFLAMMASOME

KW - CALCIFICATION

KW - SEQUESTRATION

KW - AGGREGATION

KW - CELLS

KW - SIZE

KW - FUNCTIONALIZATION

U2 - 10.1016/j.biomaterials.2013.10.041

DO - 10.1016/j.biomaterials.2013.10.041

M3 - Article

SN - 0142-9612

VL - 35

SP - 1074

EP - 1088

JO - Biomaterials

JF - Biomaterials

IS - 3

ER -