Potential proinflammatory effects of hydroxyapatite nanoparticles on endothelial cells in a monocyte–endothelial cell coculture model

Abstract

Currently, synthetic hydroxyapatite nanoparticles (HANPs) are used in nanomedicine fields. The delivery of nanomedicine to the bloodstream exposes the cardiovascular system to a potential threat. However, the possible adverse cardiovascular effects of HANPs remain unclear. Current observations using coculture models of endothelial cells and monocytes with HANPs to mimic the complex physiological functionality of the vascular system demonstrate that monocytes could play an important role in the mechanisms of endothelium dysfunction induced by the exposure to HANPs. Our transmission electron microscopy analysis revealed that both monocytes and endothelial cells could take up HANPs. Moreover, our findings demonstrated that at a subcytotoxic dose, HANPs alone did not cause direct endothelial cell injury, but they did induce an indirect activation of endothelial cells, resulting in increased interleukin-6 production and elevated adhesion molecule expression after coculture with monocytes. The potential proinflammatory effect of HANPs is largely mediated by the release of soluble factors from the activated monocytes, leading to an inflammatory response of the endothelium, which is possibly dependent on p38/c-Jun N-terminal kinase, and nuclear factor-kappa B signaling activation. The use of in vitro monocyte–endothelial cell coculture models for the biocompatibility assessment of HANPs could reveal their potential proinflammatory effects on endothelial cells, suggesting that exposure to HANPs possibly increases the risk of cardiovascular disease.

Surface modification of polymer nanoparticles with native albumin for enhancing drug delivery to solid tumors

“…In contrast, the HUVEC layer treated with PBS or IO@NP-pD-Al showed much smaller vesicles (0.07 – 0.2 μm) resembling caveolae [54]. Although individual NPs could not be identified, the large vesicles in IO@NPxAl-treated HUVEC are thought to be lysosomes filled with IO@NPxAl, given the morphological similarity to the lysosomes seen in HUVEC internalizing metal and silica particles [55, 56]. The NP content in the HUVEC layer and the TEM image indicate that a greater fraction of NPxAl was stuck in HUVEC during the transport across the cell layer as compared to NP-pD-Al.…”

Crystallinity of hydroxyapatite drives myofibroblastic activation and calcification in aortic valves

“…Other studies have postulated that interactions of cells with surfaces of HA particles are mediated by integrins on cell membranes[77,78]. HA particle uptake has been shown to induce activation in endothelial cells, with increased IL-6 production[79], as well as induction of osteogenic differentiation in human adipose-derived stem cells[80]. Additionally, it has been established that crystals of a differing size can affect cellular response[81].…”

Nano-Sized Hydroxyapatite Induces Apoptosis and Osteogenic Differentiation of Vascular Smooth Muscle Cells via JNK/c-JUN Pathway

“…Evidence from previous studies showed that nanoparticles can activate mitogen-activated protein kinase (MAPK) signaling cascade 7 in cells which include macrophages, 8 bone marrow stromal cells (BMSCs), 13 and endothelial cells (ECs). 14 We hypothesized that extracellular nHAp stimulated MAPK pathways which caused gene expression changes in SMCs. We found that JNK/c-JUN signaling pathway is critical for nHAp-induced VC.…”