Size-mediated cytotoxicity and apoptosis of hydroxyapatite nanoparticles in human hepatoma HepG2 cells

Yuan, Yuan; Liu, Changsheng; Qian, Jiangchao; Wang, Jing; Zhang, Yuan

doi:10.1016/j.biomaterials.2009.09.088

Cited by 227 publications

(174 citation statements)

References 41 publications

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“…It should be noted that phases 1 and 2 of quantum dot distribution in the cells were found earlier in the studies reported by Hoshino et al, 16 Clift et al, 20 and Jiang et al, 19 Kelf et al, 14 Williams et al, 15 and Corsi et al, 17 which showed formation of vesicular structures spread in the cytoplasm corresponding to phase 2. Phase 3, ie, localization of vesicular structures in the perinuclear region, was described by Zhang et al 22 and Xiao et al, 23 and reviewed by Parak et al 33 Phase 4 resembles the data on formation of multivesicular body-like structures and their redistribution in cytoplasm presented by Yuan et al 18 and Jiang et al 19 However, there has been no presentation of an overall picture illustrating the time-dependent nature of natural uptake and distribution of nontargeted negatively charged quantum dots in living cells.…”

Section: Discussionmentioning

confidence: 62%

“…1,11,12 Analysis of results presented in the literature reveals a very wide range of values for quantum dot internalization parameters, in particular, uptake time and intracellular localization. [13][14][15][16][17][18][19][20][21][22][23][24] This could be due to time-dependent changes in accumulation and intracellular distribution of quantum dots taking place even in a single cell line. The interpretation of results is even more complicated in the case of in vivo studies where the quantum dots would be internalized by different types of cells.…”

Section: Introductionmentioning

confidence: 99%

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Intracellular distribution of nontargeted quantum dots after natural uptake and microinjection

Damalakiene¹,

Karabanovas²,

Bagdonas³

et al. 2013

IJN

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Background:The purpose of this study was to elucidate the mechanism of natural uptake of nonfunctionalized quantum dots in comparison with microinjected quantum dots by focusing on their time-dependent accumulation and intracellular localization in different cell lines. Methods:The accumulation dynamics of nontargeted CdSe/ZnS carboxyl-coated quantum dots (emission peak 625 nm) was analyzed in NIH3T3, MCF-7, and HepG2 cells by applying the methods of confocal and steady-state fluorescence spectroscopy. Intracellular colocalization of the quantum dots was investigated by staining with Lysotracker ® . Results:The uptake of quantum dots into cells was dramatically reduced at a low temperature (4°C), indicating that the process is energy-dependent. The uptake kinetics and imaging of intracellular localization of quantum dots revealed three accumulation stages of carboxyl-coated quantum dots at 37°C, ie, a plateau stage, growth stage, and a saturation stage, which comprised four morphological phases: adherence to the cell membrane; formation of granulated clusters spread throughout the cytoplasm; localization of granulated clusters in the perinuclear region; and formation of multivesicular body-like structures and their redistribution in the cytoplasm. Diverse quantum dots containing intracellular vesicles in the range of approximately 0.5-8 µm in diameter were observed in the cytoplasm, but none were found in the nucleus. Vesicles containing quantum dots formed multivesicular body-like structures in NIH3T3 cells after 24 hours of incubation, which were Lysotracker-negative in serum-free medium and Lysotracker-positive in complete medium. The microinjected quantum dots remained uniformly distributed in the cytosol for at least 24 hours. Conclusion: Natural uptake of quantum dots in cells occurs through three accumulation stages via a mechanism requiring energy. The sharp contrast of the intracellular distribution after microinjection of quantum dots in comparison with incubation as well as the limited transfer of quantum dots from vesicles into the cytosol and vice versa support the endocytotic origin of the natural uptake of quantum dots. Quantum dots with proteins adsorbed from the culture medium had a different fate in the final stage of accumulation from that of the protein-free quantum dots, implying different internalization pathways.

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Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Intracellular distribution of nontargeted quantum dots after natural uptake and microinjection

Damalakiene¹,

Karabanovas²,

Bagdonas³

et al. 2013

IJN

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“…A previous study has indicated that the HANPs, only within the cell nucleus, could induce cytotoxicity, while the HANPs that remained in the perinuclear region or cytoplasm only caused local modifications to the morphology and structure of the cell membrane and exerted negligible inhibitory effects. 35,36,37 However, our results suggested that HANPs might interact with organelles, such as chondriosome and lysosomes (Figure 3), thus interfering with HUVEC survival and function although they concentrated in the cytoplasm (Figures 2 and 7). The uptake of NPs originated from an event of NPs adhering to the cell membrane, and this process was followed by the actual internalization via energy-dependent uptake pathways.…”

Section: Discussionmentioning

confidence: 74%

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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“…Of these characteristics, the particle size is a crucial factor which determines NP endocytosis pathway [17,18], uptake rate and efficiency [6,16,[19][20][21][22], in vitro cytotoxicity [23][24][25][26][27][28], immune responses [27][28][29][30], and the final localisation [15,31,32]. Thus size-dependent uptake of various NPs has been intensively investigated and widely reported.…”

Section: Introductionmentioning

confidence: 99%

Particle size- and number-dependent delivery to cells by layered double hydroxide nanoparticles

Dong

Parekh

2015

Journal of Colloid and Interface Science

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a b s t r a c tIt is well known that delivery efficiency to cells is highly dependent on particle size and the administered dose. However, there is a marked discrepancy in many reports, mainly due to the inconsistency in assessment of various parameters. In this particular research, we designed experiments using layered double hydroxide nanoparticles (LDH NPs) to specifically elucidate the effect of particle size, dose and dye loading manner on cellular uptake. Using the number of LDH NPs taken up by HCT-116 cells as the indicator of delivery efficiency, we found that (1) the size of sheet-like LDH in the range of 40-100 nm did not significantly affect their cellular uptake; (2) cellular uptake of 40 and 100 nm LDH NPs was increased proportionally to the number concentration below a critical value, but remained relatively constant beyond the critical value; and (3) the effect of the dye loading manner is mainly dependent on the loading capacity or yield. In particular, the loading capacity is determined by the NP specific surface area. This research may be extended to a larger size range to examine the size effect, but suggests that it is necessary to set up a protocol to evaluate the effects of NP's physicochemical properties on the cellular delivery efficiency.

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Size-mediated cytotoxicity and apoptosis of hydroxyapatite nanoparticles in human hepatoma HepG2 cells

Cited by 227 publications

References 41 publications

Intracellular distribution of nontargeted quantum dots after natural uptake and microinjection

Intracellular distribution of nontargeted quantum dots after natural uptake and microinjection

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

Particle size- and number-dependent delivery to cells by layered double hydroxide nanoparticles

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