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

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.

Investigating the role of Hedgehog/GLI1 signaling in glioblastoma cell response to temozolomide

“…Therapeutic synergy between GLI1 silencing and TMZ was assessed using previously reported methods [ 60 ]. For each group co-treated with siGLI1 and TMZ, a projected additive effect was calculated by multiplying the fraction of metabolic activity reduced by GLI1 silencing alone by the fraction of metabolic activity reduced by each TMZ dose.…”

Photothermal therapeutic application of gold nanorods-porphyrin-trastuzumab complexes in HER2-positive breast cancer

“…This kind of heat energy can produce specific hyperthermia within the local part, ultimately leading to cell death 16 . For thermal applications, several types of gold nanoparticles have been performed to target cancer cells, such as gold nanoshells 11 17 18 , hollow gold nanospheres 19 , nanocages 20 , and nanorods 21 22 . In this research, we constructed a novel complex using gold nanorods (GNRs) coated with porphyrin as well as anti-HER2 antibody (trastuzumab) called GNRs-porphyrin-trastuzumab complexes (TGNs) and investigated the efficiency of this complex in targeting and photothermally ablating of HER2-positive breast cancer in vitro and vivo .…”

Fluorescent, Plasmonic, and Radiotherapeutic Properties of the 177Lu–Dendrimer-AuNP–Folate–Bombesin Nanoprobe Located Inside Cancer Cells

“…The Au4f spectrum was statistically analyzed using the Origin 8.1 software. The best fit was achieved for 4 peaks with a multipeak model and the Gaussian function with a correlation factor R 2 of .987 (DenAuNP–folate–bombesin), and for 6 peaks and the Lorentzian function with R 2 = .994 for the DenAuNP–folate–bombesin cell.…”