Limits...
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

(A) Proposed mechanism of chemosensitization provided by nanoshell (NS)-mediated photothermal therapy. When cancer cells are incubated with NSs and doxorubicin and subsequently irradiated with near-infrared light, the heat produced by the NSs increases cell membrane permeability, resulting in increased doxorubicin accumulation in the cells. (B) Analysis of rhodamine 123 uptake by cells exposed to light, NSs, or both light and NSs. Relative fluorescence in each group is normalized to cells exposed to only media. The error bars represent standard deviation across six technical replicates. Differences in rhodamine fluorescence between groups were analyzed by ANOVA with post hoc Tukey. *P<0.02 for all comparisons to media only, light only, and NS only.Abbreviations: NIR, near infrared; ANOVA, analysis of variance.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4644159&req=5

f3-ijn-10-6931: (A) Proposed mechanism of chemosensitization provided by nanoshell (NS)-mediated photothermal therapy. When cancer cells are incubated with NSs and doxorubicin and subsequently irradiated with near-infrared light, the heat produced by the NSs increases cell membrane permeability, resulting in increased doxorubicin accumulation in the cells. (B) Analysis of rhodamine 123 uptake by cells exposed to light, NSs, or both light and NSs. Relative fluorescence in each group is normalized to cells exposed to only media. The error bars represent standard deviation across six technical replicates. Differences in rhodamine fluorescence between groups were analyzed by ANOVA with post hoc Tukey. *P<0.02 for all comparisons to media only, light only, and NS only.Abbreviations: NIR, near infrared; ANOVA, analysis of variance.

Mentions: We hypothesized that low-dose PTT could increase cell membrane permeability to enhance drug accumulation in IBC cells (Figure 3A). To investigate the effect of low-dose PTT on drug uptake, we compared rhodamine 123 fluorescence in cells treated with: 1) media only, 2) NIR light only, 3) nanoshells only, or 4) PTT (ie, nanoshells and NIR light). Flow cytometry was used to determine the mean fluorescence of each group as described in the “Materials and methods” section. As shown in Figure 3B, cells exposed to only media, NIR light, or nano-shells displayed similar levels of rhodamine fluorescence, and the differences between groups were not significant according to ANOVA. Thus, neither light nor nanoshells alone are sufficient to enhance rhodamine uptake in cells. In contrast, cells treated with PTT displayed 56% higher rhodamine fluorescence than the media only group, confirming that PTT can enhance dye accumulation in cells. An ANOVA with post hoc Tukey validated that the fluorescence signal in the PTT-treated cells was significantly different from that in all other groups. The P-value for each comparison was: P=0.0025 for PTT versus media, P=0.0029 for PTT versus light only, and P=0.0112 for PTT versus nanoshells only.


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

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

(A) Proposed mechanism of chemosensitization provided by nanoshell (NS)-mediated photothermal therapy. When cancer cells are incubated with NSs and doxorubicin and subsequently irradiated with near-infrared light, the heat produced by the NSs increases cell membrane permeability, resulting in increased doxorubicin accumulation in the cells. (B) Analysis of rhodamine 123 uptake by cells exposed to light, NSs, or both light and NSs. Relative fluorescence in each group is normalized to cells exposed to only media. The error bars represent standard deviation across six technical replicates. Differences in rhodamine fluorescence between groups were analyzed by ANOVA with post hoc Tukey. *P<0.02 for all comparisons to media only, light only, and NS only.Abbreviations: NIR, near infrared; ANOVA, analysis of variance.
© Copyright Policy
Related In: Results  -  Collection

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

f3-ijn-10-6931: (A) Proposed mechanism of chemosensitization provided by nanoshell (NS)-mediated photothermal therapy. When cancer cells are incubated with NSs and doxorubicin and subsequently irradiated with near-infrared light, the heat produced by the NSs increases cell membrane permeability, resulting in increased doxorubicin accumulation in the cells. (B) Analysis of rhodamine 123 uptake by cells exposed to light, NSs, or both light and NSs. Relative fluorescence in each group is normalized to cells exposed to only media. The error bars represent standard deviation across six technical replicates. Differences in rhodamine fluorescence between groups were analyzed by ANOVA with post hoc Tukey. *P<0.02 for all comparisons to media only, light only, and NS only.Abbreviations: NIR, near infrared; ANOVA, analysis of variance.
Mentions: We hypothesized that low-dose PTT could increase cell membrane permeability to enhance drug accumulation in IBC cells (Figure 3A). To investigate the effect of low-dose PTT on drug uptake, we compared rhodamine 123 fluorescence in cells treated with: 1) media only, 2) NIR light only, 3) nanoshells only, or 4) PTT (ie, nanoshells and NIR light). Flow cytometry was used to determine the mean fluorescence of each group as described in the “Materials and methods” section. As shown in Figure 3B, cells exposed to only media, NIR light, or nano-shells displayed similar levels of rhodamine fluorescence, and the differences between groups were not significant according to ANOVA. Thus, neither light nor nanoshells alone are sufficient to enhance rhodamine uptake in cells. In contrast, cells treated with PTT displayed 56% higher rhodamine fluorescence than the media only group, confirming that PTT can enhance dye accumulation in cells. An ANOVA with post hoc Tukey validated that the fluorescence signal in the PTT-treated cells was significantly different from that in all other groups. The P-value for each comparison was: P=0.0025 for PTT versus media, P=0.0029 for PTT versus light only, and P=0.0112 for PTT versus nanoshells only.

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