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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

Evaluation of the impact of photothermal therapy on SUM149 cells.Notes: Top: Silver staining reveals nanoshells bound to cells; (A) cells without nanoshells, (B) cells with nanoshells. Scale bar =150 μm. Bottom: Only cells exposed to both nanoshells and light displayed increased membrane permeability, evidenced by red EthD-1 fluorescence. Green fluorescence indicates viable cells with an intact membrane; (C) cells without nanoshells + near-infrared (NIR) light, (D) cells with nanoshells + NIR light. Within (D), cells outside the light exposed region indicated by the white dotted line remain viable confirming nanoshells alone are safe. Scale bar =500 μm.
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f2-ijn-10-6931: Evaluation of the impact of photothermal therapy on SUM149 cells.Notes: Top: Silver staining reveals nanoshells bound to cells; (A) cells without nanoshells, (B) cells with nanoshells. Scale bar =150 μm. Bottom: Only cells exposed to both nanoshells and light displayed increased membrane permeability, evidenced by red EthD-1 fluorescence. Green fluorescence indicates viable cells with an intact membrane; (C) cells without nanoshells + near-infrared (NIR) light, (D) cells with nanoshells + NIR light. Within (D), cells outside the light exposed region indicated by the white dotted line remain viable confirming nanoshells alone are safe. Scale bar =500 μm.

Mentions: SUM149 IBC cells were incubated with nanoshells and silver stained in order to demonstrate effective binding of the nanoparticles to the cells. Figure 2A displays cells that were not exposed to nanoshells, while Figure 2B shows nanoshell-treated cells. The positive stain (dark regions) in Figure 2B confirms that nanoshells were able to adhere nonspecifically to SUM149 cells. The level of nanoshells present was sufficient to enable cellular membrane damage via PTT (Figure 2C and D). Upon NIR irradiation at 80 W/cm2 for 3 minutes, SUM149 cells not exposed to nanoshells maintained viability and membrane integrity, indicated by positive green calcein fluorescence and lack of red EthD-1 fluorescence (Figure 2C). In contrast, cells incubated with nanoshells prior to light exposure experienced loss of membrane integrity within the laser spot (outlined by the white dotted line), indicated by red EthD-1 fluorescence (Figure 2D). Cells outside the laser spot maintained their viability and membrane integrity, confirming that nanoshells alone are not cytotoxic.


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

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

Evaluation of the impact of photothermal therapy on SUM149 cells.Notes: Top: Silver staining reveals nanoshells bound to cells; (A) cells without nanoshells, (B) cells with nanoshells. Scale bar =150 μm. Bottom: Only cells exposed to both nanoshells and light displayed increased membrane permeability, evidenced by red EthD-1 fluorescence. Green fluorescence indicates viable cells with an intact membrane; (C) cells without nanoshells + near-infrared (NIR) light, (D) cells with nanoshells + NIR light. Within (D), cells outside the light exposed region indicated by the white dotted line remain viable confirming nanoshells alone are safe. Scale bar =500 μm.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-10-6931: Evaluation of the impact of photothermal therapy on SUM149 cells.Notes: Top: Silver staining reveals nanoshells bound to cells; (A) cells without nanoshells, (B) cells with nanoshells. Scale bar =150 μm. Bottom: Only cells exposed to both nanoshells and light displayed increased membrane permeability, evidenced by red EthD-1 fluorescence. Green fluorescence indicates viable cells with an intact membrane; (C) cells without nanoshells + near-infrared (NIR) light, (D) cells with nanoshells + NIR light. Within (D), cells outside the light exposed region indicated by the white dotted line remain viable confirming nanoshells alone are safe. Scale bar =500 μm.
Mentions: SUM149 IBC cells were incubated with nanoshells and silver stained in order to demonstrate effective binding of the nanoparticles to the cells. Figure 2A displays cells that were not exposed to nanoshells, while Figure 2B shows nanoshell-treated cells. The positive stain (dark regions) in Figure 2B confirms that nanoshells were able to adhere nonspecifically to SUM149 cells. The level of nanoshells present was sufficient to enable cellular membrane damage via PTT (Figure 2C and D). Upon NIR irradiation at 80 W/cm2 for 3 minutes, SUM149 cells not exposed to nanoshells maintained viability and membrane integrity, indicated by positive green calcein fluorescence and lack of red EthD-1 fluorescence (Figure 2C). In contrast, cells incubated with nanoshells prior to light exposure experienced loss of membrane integrity within the laser spot (outlined by the white dotted line), indicated by red EthD-1 fluorescence (Figure 2D). Cells outside the laser spot maintained their viability and membrane integrity, confirming that nanoshells alone are not cytotoxic.

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