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Nanoshell-mediated photothermal therapy can enhance chemotherapy in inflammatory breast cancer cells.

Fay BL, Melamed JR, Day ES - Int J Nanomedicine (2015)

Bottom Line: The results confirmed that nanoshell-mediated PTT could increase membrane permeability in SUM149 cells.Analyzing rhodamine 123 fluorescence in cells via flow cytometry confirmed that increased membrane permeability caused by PTT could enhance drug accumulation in cells.These data indicate that nanoshell-mediated PTT is a viable strategy to potentiate the effects of chemotherapy and warrant further investigation of this approach using other drugs and cancer subtypes.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Engineering, University of Delaware, Newark, DE, USA.

ABSTRACT
Nanoshell-mediated photothermal therapy (PTT) is currently being investigated as a standalone therapy for the treatment of cancer. The cellular effects of PTT include loss of membrane integrity, so we hypothesized that nanoshell-mediated PTT could potentiate the cytotoxicity of chemotherapy by improving drug accumulation in cancer cells. In this work, we validated our hypothesis using doxorubicin as a model drug and SUM149 inflammatory breast cancer cells as a model cancer subtype. In initial studies, SUM149 cells were exposed to nano-shells and near-infrared light and then stained with ethidium homodimer-1, which is excluded from cells with an intact plasma membrane. The results confirmed that nanoshell-mediated PTT could increase membrane permeability in SUM149 cells. In complementary experiments, SUM149 cells treated with nanoshells, near-infrared light, or a combination of the two to yield low-dose PTT were exposed to fluorescent rhodamine 123. Analyzing rhodamine 123 fluorescence in cells via flow cytometry confirmed that increased membrane permeability caused by PTT could enhance drug accumulation in cells. This was validated using fluorescence microscopy to assess intracellular distribution of doxorubicin. In succeeding experiments, SUM149 cells were exposed to subtherapeutic levels of doxorubicin, low-dose PTT, or a combination of the two treatments to determine whether the additional drug uptake induced by PTT is sufficient to enhance cell death. Analysis revealed minimal loss of viability relative to controls in cells exposed to subtherapeutic levels of doxorubicin, 15% loss of viability in cells exposed to low-dose PTT, and 35% loss of viability in cells exposed to combination therapy. These data indicate that nanoshell-mediated PTT is a viable strategy to potentiate the effects of chemotherapy and warrant further investigation of this approach using other drugs and cancer subtypes.

No MeSH data available.


Related in: MedlinePlus

Viability of cells treated with doxorubicin (dox), photothermal therapy (PTT), or combination therapy normalized to the media control group.Notes: The error bars represent the standard deviation across four biological replicates of the experiment. Groups with significant differences in viability according to ANOVA with post hoc Tukey are denoted with asterisks. *P<0.01, **P<0.0001, ***P=0.0003.Abbreviation: ANOVA, analysis of variance.
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f5-ijn-10-6931: Viability of cells treated with doxorubicin (dox), photothermal therapy (PTT), or combination therapy normalized to the media control group.Notes: The error bars represent the standard deviation across four biological replicates of the experiment. Groups with significant differences in viability according to ANOVA with post hoc Tukey are denoted with asterisks. *P<0.01, **P<0.0001, ***P=0.0003.Abbreviation: ANOVA, analysis of variance.

Mentions: To investigate the chemosensitization effect of PTT, four experimental groups were compared: cells incubated with: 1) media only, 2) 0.75 μM dox (an intentionally subtherapeutic dose), 3) 1×109 nanoshells, and 4) both 1×109 nanoshells and 0.75 μM dox. Each group was exposed to NIR irradiation at 5.5 W/cm2 in the entire well for 3 minutes. After incubating overnight, cell viability was assessed with an AlamarBlue assay and results were normalized to the media control group (Figure 5). Cells incubated with the intentionally sub-therapeutic dose of dox experienced minimal cytotoxicity, as indicated by viability of 97.7%±3.7%. Cells treated with only low-dose PTT demonstrated viability of 84.8%±2.9%. Finally, cells that received dox treatment and PTT demonstrated 64.5%±8.1% viability, which is ~20% less than the viability observed after PTT alone. An ANOVA with post hoc Tukey revealed that the viabilities of cells treated with either media or dox were significantly different from the viabilities of cells treated with standalone PTT (P<0.01) or combination PTT plus dox (P<0.001). In addition, the PTT and PTT plus dox groups were significantly different from each other, with a P-value of 0.0003.


Nanoshell-mediated photothermal therapy can enhance chemotherapy in inflammatory breast cancer cells.

Fay BL, Melamed JR, Day ES - Int J Nanomedicine (2015)

Viability of cells treated with doxorubicin (dox), photothermal therapy (PTT), or combination therapy normalized to the media control group.Notes: The error bars represent the standard deviation across four biological replicates of the experiment. Groups with significant differences in viability according to ANOVA with post hoc Tukey are denoted with asterisks. *P<0.01, **P<0.0001, ***P=0.0003.Abbreviation: ANOVA, analysis of variance.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644159&req=5

f5-ijn-10-6931: Viability of cells treated with doxorubicin (dox), photothermal therapy (PTT), or combination therapy normalized to the media control group.Notes: The error bars represent the standard deviation across four biological replicates of the experiment. Groups with significant differences in viability according to ANOVA with post hoc Tukey are denoted with asterisks. *P<0.01, **P<0.0001, ***P=0.0003.Abbreviation: ANOVA, analysis of variance.
Mentions: To investigate the chemosensitization effect of PTT, four experimental groups were compared: cells incubated with: 1) media only, 2) 0.75 μM dox (an intentionally subtherapeutic dose), 3) 1×109 nanoshells, and 4) both 1×109 nanoshells and 0.75 μM dox. Each group was exposed to NIR irradiation at 5.5 W/cm2 in the entire well for 3 minutes. After incubating overnight, cell viability was assessed with an AlamarBlue assay and results were normalized to the media control group (Figure 5). Cells incubated with the intentionally sub-therapeutic dose of dox experienced minimal cytotoxicity, as indicated by viability of 97.7%±3.7%. Cells treated with only low-dose PTT demonstrated viability of 84.8%±2.9%. Finally, cells that received dox treatment and PTT demonstrated 64.5%±8.1% viability, which is ~20% less than the viability observed after PTT alone. An ANOVA with post hoc Tukey revealed that the viabilities of cells treated with either media or dox were significantly different from the viabilities of cells treated with standalone PTT (P<0.01) or combination PTT plus dox (P<0.001). In addition, the PTT and PTT plus dox groups were significantly different from each other, with a P-value of 0.0003.

Bottom Line: The results confirmed that nanoshell-mediated PTT could increase membrane permeability in SUM149 cells.Analyzing rhodamine 123 fluorescence in cells via flow cytometry confirmed that increased membrane permeability caused by PTT could enhance drug accumulation in cells.These data indicate that nanoshell-mediated PTT is a viable strategy to potentiate the effects of chemotherapy and warrant further investigation of this approach using other drugs and cancer subtypes.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Engineering, University of Delaware, Newark, DE, USA.

ABSTRACT
Nanoshell-mediated photothermal therapy (PTT) is currently being investigated as a standalone therapy for the treatment of cancer. The cellular effects of PTT include loss of membrane integrity, so we hypothesized that nanoshell-mediated PTT could potentiate the cytotoxicity of chemotherapy by improving drug accumulation in cancer cells. In this work, we validated our hypothesis using doxorubicin as a model drug and SUM149 inflammatory breast cancer cells as a model cancer subtype. In initial studies, SUM149 cells were exposed to nano-shells and near-infrared light and then stained with ethidium homodimer-1, which is excluded from cells with an intact plasma membrane. The results confirmed that nanoshell-mediated PTT could increase membrane permeability in SUM149 cells. In complementary experiments, SUM149 cells treated with nanoshells, near-infrared light, or a combination of the two to yield low-dose PTT were exposed to fluorescent rhodamine 123. Analyzing rhodamine 123 fluorescence in cells via flow cytometry confirmed that increased membrane permeability caused by PTT could enhance drug accumulation in cells. This was validated using fluorescence microscopy to assess intracellular distribution of doxorubicin. In succeeding experiments, SUM149 cells were exposed to subtherapeutic levels of doxorubicin, low-dose PTT, or a combination of the two treatments to determine whether the additional drug uptake induced by PTT is sufficient to enhance cell death. Analysis revealed minimal loss of viability relative to controls in cells exposed to subtherapeutic levels of doxorubicin, 15% loss of viability in cells exposed to low-dose PTT, and 35% loss of viability in cells exposed to combination therapy. These data indicate that nanoshell-mediated PTT is a viable strategy to potentiate the effects of chemotherapy and warrant further investigation of this approach using other drugs and cancer subtypes.

No MeSH data available.


Related in: MedlinePlus