Differential Cytotoxicity and Particle Action of Hydroxyapatite Nanoparticles in Human Cancer Cells

Tang, Wei; Yuan, Yuan; Liu, Changsheng; Wu, Yuequn; Lu, Xun; Qian, Jiangchao

doi:10.2217/nnm.12.217

Cited by 89 publications

(71 citation statements)

References 37 publications

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“…E.g., a recent study on the impact of amorphous SNPs in three pairs of murine/human cell lines (lung epithelium, macrophages, and colon epithelium) found that macrophages were the most sensitive cell type among the three pairs, whereas murine cell lines were more sensitive than comparable human cell lines . Another study revealed that HUVECs were more sensitive than HeLa cells upon 310 nm SNPs exposure, and we also demonstrated differential toxicity of hydroxyapatite nanoparticles in human cancer cells with an order of MGC80–3 > HepG2 > HeLa . These results clearly show that cytotoxic effects of nanoparticles cannot be generalized and transferred from one cell type to another.…”

Section: Discussionsupporting

confidence: 68%

Cytotoxicity and Cellular Uptake of Amorphous Silica Nanoparticles in Human Cancer Cells

Tang

Wang

et al. 2015

Part. Part. Syst. Charact.

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The cytotoxic effects of silica nanoparticles (SNPs) on different human cancer cells, as well as the uptake kinetics and pathways of SNPs have been studied here. SNPs with the diameter of ≈20 nm induced a dose‐dependent cytotoxicity in both gastric cancer cells (MGC80–3) and cervical adenocarcinoma epithelial cells (HeLa), but MGC80–3 cells were more susceptible to the cytotoxic effect induced by SNPs. Changes in the nuclear morphology and flow cytometric analysis with annexin V/PI double staining show that SNPs induced a higher degree of apoptosis in MGC80–3 cells. Accordingly, more remarkable reactive oxygen species (ROS) burst is detected in SNP‐treated MGC80–3 cells. Using fluorescein isothiocyanate (FITC)‐labeled SNPs and flow cytometry, it is found that the uptake of SNPs is more efficient in MGC80–3 than in HeLa cells. SNPs are internalized into both cancer cells through energy‐dependent pathway. Inhibitor studies with dynasore and methyl‐β‐cyclodextrin show that these cancer cells took up 20 nm SNPs mainly through the caveolin‐mediated endocytosis, while in HeLa cells SNPs internalization was also via dynamin‐dependent clathrin‐mediated pathway. These findings indicate that SNPs cause differential cytotoxic effects in different human cancer cells, which might be related to the uptake process and efficiency toward these cancer cells.

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Section: Discussionsupporting

confidence: 68%

Cytotoxicity and Cellular Uptake of Amorphous Silica Nanoparticles in Human Cancer Cells

Tang

Wang

et al. 2015

Part. Part. Syst. Charact.

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“…The analysis of reactive oxide species in the conditioned media revealed no statistically significant differences between the analysed groups. It is known that hydroxyapatite may induce the formation of reactive oxygen species, however, its cytotoxicity may differ between different cell types, as shown previously [28]. The supernatants of cells cultured on biomaterial 4, 6 and 8 under chondrogenic and osteogenic conditions had lower concentrations of nitric oxide than the respective non-stimulated control groups.…”

Section: Quantitative Analysis Of Cellular Oxidative Stress Factorssupporting

confidence: 54%

Biphasic Polyurethane/Polylactide Sponges Doped with Nano-Hydroxyapatite (nHAp) Combined with Human Adipose-Derived Mesenchymal Stromal Stem Cells for Regenerative Medicine Applications

et al. 2016

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Cartilage and bone tissue injuries are common targets in regenerative medicine. The degeneration of cartilage tissue results in tissue loss with a limited ability to regenerate. However, the application of mesenchymal stem cells in the course of such condition makes it possible to manage this disorder by improving the structure of the remaining tissue and even stimulating its regeneration. Nevertheless, in the case of significant tissue loss, standard local injection of cell suspensions is insufficient, due to the low engraftment of transplanted cells. Introduction of mesenchymal stem cells on the surface of a compatible biomaterial can be a promising tool for inducing the regeneration by both retaining the cells at the desired site and filling the tissue gap. In order to obtain such a cell-biomaterial hybrid, we developed complex, biphasic polymer blend biomaterials composed of various polyurethane (PU)-to-polylactide (PLA) ratios, and doped with different concentrations of nano-hydroxyapatite (nHAp). We have determined the optimal blend composition and nano-hydroxyapatite concentration for adipose mesenchymal stem cells cultured on the biomaterial. We applied biological in vitro techniques, including cell viability assay, determination of oxidative stress factors level, osteogenic and chondrogenic differentiation potentials as well as cell proteomic analysis. We have shown that the optimal composition of biphasic scaffold was 20:80 of PU:PLA with 20% of nHAp for osteogenic differentiation, and 80:20 of PU:PLA with 10% of nHAp for chondrogenic differentiation, which suggest the optimal composition of final biphasic implant for regenerative medicine applications.

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“…The cytotoxic effect of np20 and np80 on HUVECs could be attributed to the induction of oxidative stress by HANPs as well as elevated intracellular calcium concentration due to substantial uptake of HANPs (Figures 3-5). 30,31 To date, the cytotoxicity of HANPs still remains a matter of debate. It has also been reported that HANPs were compatible to mouse bone marrow mesenchymal stem cells.…”

Section: Discussionmentioning

confidence: 99%

Interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway

Shi¹,

Zhou²,

Huang³

et al. 2017

IJN

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Nano-hydroxyapatite (nano-HAP) has been proposed as a better candidate for bone tissue engineering; however, the interactions of nano-HAP with endothelial cells are currently unclear. In this study, HAP nanoparticles (HANPs; 20 nm np20 and 80 nm np80) and micro-sized HAP particles (m-HAP; 12 μm) were employed to explore and characterize cellular internalization, subcellular distribution, effects of HANPs on endothelial cell function and underlying mechanisms using human umbilical vein endothelial cells (HUVECs) as an in vitro model. It was found that HANPs were able to accumulate in the cytoplasm, and both adhesion and uptake of the HANPs followed a function of time; compared to np80, more np20 had been uptaken at the end of the observation period. HANPs were mainly uptaken via clathrin- and caveolin-mediated endocytosis, while macropinocytosis was the main pathway for m-HAP uptake. Unexpectedly, exposure to HANPs suppressed the angiogenic ability of HUVECs in terms of cell viability, cell cycle, apoptosis response, migration and capillary-like tube formation. Strikingly, HANPs reduced the synthesis of nitric oxide (NO) in HUVECs, which was associated with the inhibition of phosphatidylinositol 3-kinase (PI3K) and phosphorylation of eNOS. These findings provide additional insights into specific biological responses as HANPs interface with endothelial cells.

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Differential Cytotoxicity and Particle Action of Hydroxyapatite Nanoparticles in Human Cancer Cells

Cited by 89 publications

References 37 publications

Cytotoxicity and Cellular Uptake of Amorphous Silica Nanoparticles in Human Cancer Cells

Cytotoxicity and Cellular Uptake of Amorphous Silica Nanoparticles in Human Cancer Cells

Biphasic Polyurethane/Polylactide Sponges Doped with Nano-Hydroxyapatite (nHAp) Combined with Human Adipose-Derived Mesenchymal Stromal Stem Cells for Regenerative Medicine Applications

Interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway

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