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Cell type-dependent changes in CdSe/ZnS quantum dot uptake and toxic endpoints.

Manshian BB, Soenen SJ, Al-Ali A, Brown A, Hondow N, Wills J, Jenkins GJ, Doak SH - Toxicol. Sci. (2015)

Bottom Line: Following thorough physicochemical characterization, cellular uptake, cytotoxicity, and gross chromosomal damage were measured.BEAS-2B cells demonstrated the highest level of QDs uptake yet displayed a strong resilience with minimal genotoxicity following exposure to these NPs.Thus, this study demonstrates that in addition to nanomaterial physicochemical characterization, a clear understanding of cell type-dependent variation in uptake coupled to the inherently different capacities of the cell types to cope with exposure to these exogenous materials are all required to predict genotoxicity.

View Article: PubMed Central - PubMed

Affiliation: *Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, Department of Medicine, Biomedical NMR Unit-MoSAIC, KU Leuven, B-3000 Leuven, Belgium and Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK *Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, Department of Medicine, Biomedical NMR Unit-MoSAIC, KU Leuven, B-3000 Leuven, Belgium and Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK s.h.doak@swansea.ac.uk.

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ImageStream cellular uptake analysis following QD exposure. A, HFF-1; B, BEAS-2B; and C, TK6 cells exposed to amine- and carboxyl-QD for 24 h in low serum or high serum containing media. Each graph is accompanied with representative results of cellular uptake images captured with ImageStream. Where appropriate, the degree of significance is indicated (*P < 0.05, **P < 0.01, ***P < 0.001).
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kfv002-F1: ImageStream cellular uptake analysis following QD exposure. A, HFF-1; B, BEAS-2B; and C, TK6 cells exposed to amine- and carboxyl-QD for 24 h in low serum or high serum containing media. Each graph is accompanied with representative results of cellular uptake images captured with ImageStream. Where appropriate, the degree of significance is indicated (*P < 0.05, **P < 0.01, ***P < 0.001).

Mentions: Clear differences in relative intracellular fluorescence intensity were seen between the 3 cell lines exposed to each of the test QDs (Fig. 1). In general, fluorescence intensity, hence uptake levels, was much higher in BEAS-2B and TK6 cells compared with the HFF-1 cells. For BEAS-2B cells, clear concentration-dependent uptake could be seen for both amine and carboxyl-QDs, where this was not the case for HFF-1 cells. Carboxylated QDs demonstrated higher uptake than amine-QDs. For example, in BEAS-2B cells exposed to 15 nM of carboxyl-QDs, relative fluorescence intensity values of over 3000% were obtained, compared with 1100% for BEAS-2B cells exposed to an equivalent concentration of amine-QDs in full serum conditions. Carboxyl-QDs were readily taken up by all 3 cell lines with the highest uptake seen in BEAS-2B followed by TK6 and then HFF-1 cells. In TK6 cells this corresponded to a 2900-fold increase in cellular fluorescence in 1% serum conditions compared with the controls. Uptake of the same QDs was much less in 10% serum conditions (only 400-fold). No significant uptake was noted in these cells when exposed to the amine-QD. For both QDs serum conditions (reduced vs full) did not play a major role in cellular uptake levels except for TK6 cells exposed to carboxyl-QDs where significantly lower uptake was observed in full serum compared with reduced serum containing media (a > 20-fold drop of intensity between reduced and full serum) (Fig. 1C). Uptake levels in HFF-1 cells were substantially lower than the other 2 cell types and were not significantly different from negative controls except following exposure to carboxyl-QDs, which were significantly internalized at 7.5 and 15 nM concentrations in full and reduced serum conditions (Fig. 1A). Thus, the order of increasing cellular uptake based on cell line and QD surface coating type was BEAS-2B > TK6 > HFF-1 and carboxyl-QDs > amine-QDs, respectively.FIG. 1.


Cell type-dependent changes in CdSe/ZnS quantum dot uptake and toxic endpoints.

Manshian BB, Soenen SJ, Al-Ali A, Brown A, Hondow N, Wills J, Jenkins GJ, Doak SH - Toxicol. Sci. (2015)

ImageStream cellular uptake analysis following QD exposure. A, HFF-1; B, BEAS-2B; and C, TK6 cells exposed to amine- and carboxyl-QD for 24 h in low serum or high serum containing media. Each graph is accompanied with representative results of cellular uptake images captured with ImageStream. Where appropriate, the degree of significance is indicated (*P < 0.05, **P < 0.01, ***P < 0.001).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4372665&req=5

kfv002-F1: ImageStream cellular uptake analysis following QD exposure. A, HFF-1; B, BEAS-2B; and C, TK6 cells exposed to amine- and carboxyl-QD for 24 h in low serum or high serum containing media. Each graph is accompanied with representative results of cellular uptake images captured with ImageStream. Where appropriate, the degree of significance is indicated (*P < 0.05, **P < 0.01, ***P < 0.001).
Mentions: Clear differences in relative intracellular fluorescence intensity were seen between the 3 cell lines exposed to each of the test QDs (Fig. 1). In general, fluorescence intensity, hence uptake levels, was much higher in BEAS-2B and TK6 cells compared with the HFF-1 cells. For BEAS-2B cells, clear concentration-dependent uptake could be seen for both amine and carboxyl-QDs, where this was not the case for HFF-1 cells. Carboxylated QDs demonstrated higher uptake than amine-QDs. For example, in BEAS-2B cells exposed to 15 nM of carboxyl-QDs, relative fluorescence intensity values of over 3000% were obtained, compared with 1100% for BEAS-2B cells exposed to an equivalent concentration of amine-QDs in full serum conditions. Carboxyl-QDs were readily taken up by all 3 cell lines with the highest uptake seen in BEAS-2B followed by TK6 and then HFF-1 cells. In TK6 cells this corresponded to a 2900-fold increase in cellular fluorescence in 1% serum conditions compared with the controls. Uptake of the same QDs was much less in 10% serum conditions (only 400-fold). No significant uptake was noted in these cells when exposed to the amine-QD. For both QDs serum conditions (reduced vs full) did not play a major role in cellular uptake levels except for TK6 cells exposed to carboxyl-QDs where significantly lower uptake was observed in full serum compared with reduced serum containing media (a > 20-fold drop of intensity between reduced and full serum) (Fig. 1C). Uptake levels in HFF-1 cells were substantially lower than the other 2 cell types and were not significantly different from negative controls except following exposure to carboxyl-QDs, which were significantly internalized at 7.5 and 15 nM concentrations in full and reduced serum conditions (Fig. 1A). Thus, the order of increasing cellular uptake based on cell line and QD surface coating type was BEAS-2B > TK6 > HFF-1 and carboxyl-QDs > amine-QDs, respectively.FIG. 1.

Bottom Line: Following thorough physicochemical characterization, cellular uptake, cytotoxicity, and gross chromosomal damage were measured.BEAS-2B cells demonstrated the highest level of QDs uptake yet displayed a strong resilience with minimal genotoxicity following exposure to these NPs.Thus, this study demonstrates that in addition to nanomaterial physicochemical characterization, a clear understanding of cell type-dependent variation in uptake coupled to the inherently different capacities of the cell types to cope with exposure to these exogenous materials are all required to predict genotoxicity.

View Article: PubMed Central - PubMed

Affiliation: *Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, Department of Medicine, Biomedical NMR Unit-MoSAIC, KU Leuven, B-3000 Leuven, Belgium and Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK *Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, Department of Medicine, Biomedical NMR Unit-MoSAIC, KU Leuven, B-3000 Leuven, Belgium and Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK s.h.doak@swansea.ac.uk.

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Related in: MedlinePlus