Synergistic Effects of Cisplatin Chemotherapy and Gold Nanorod-Mediated Hyperthermia on Ovarian Cancer Cells and Tumors

Mehtala, Jonathan G.; Torregrosa-Allen, Sandra; Elzey, Bennett D.; Jeon, Mansik; Kim, Chulhong; Wei, Alexander

doi:10.2217/nnm.13.209

Cited by 47 publications

(26 citation statements)

References 65 publications

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“…17 A second study demonstrated that mild hyperthermia mediated by gold nanorods could promote apoptotic signaling in cancer cells to provide synergy with cisplatin both in vitro and in vivo. 18 This finding was in agreement with a previous study that revealed synergy between nanorod-mediated hyperthermia and cisplatin. 19 Here, we aimed to expand upon this exciting field of study by demonstrating that nanoshell-mediated PTT could sensitize cancer cells to subtherapeutic doses of doxorubicin (dox).…”

Section: Introductionsupporting

confidence: 93%

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

Fay¹,

Melamed²,

Day³

2015

IJN

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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.

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Section: Introductionsupporting

confidence: 93%

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

Fay¹,

Melamed²,

Day³

2015

IJN

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“…The significant increase of PTT and external MHT on the efficacy of these drugs, reported in previous publications, lends support to this explanation [11, 13, 35]. …”

Section: Resultssupporting

confidence: 70%

Enhancing the effects of chemotherapy by combined macrophage-mediated photothermal therapy (PTT) and photochemical internalization (PCI)

Nair

Christie

et al. 2018

Lasers Med Sci

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Light-based treatment modalities such as photothermal therapy (PTT) or photochemical internalization (PCI) have been well documented both experimentally and clinically to enhance the efficacy of chemotherapy. The main purpose of this study was to examine the cytotoxic effects of silica-gold nanoshell (AuNS)-loaded macrophage-mediated (Ma) PTT and bleomycin BLM-PCI on monolayers of squamous cell carcinoma cells. The two modalities were applied separately and in simultaneous combination. Two different wavelengths of light were employed simultaneously, one to activate a highly efficient PCI photosensitizer, AlPcSa (670 nm) and the other for the Ma-mediated PTT (810 nm), to evaluate the combined effects of these modalities. The results clearly demonstrated that macrophages could ingest sufficient numbers of silica-gold nanoshells for efficient near infrared (NIR) activated PTT. A significant synergistic effect of simultaneously applied combined PTT and PCI, compared to each modality applied separately, was achieved. Light-driven therapies have the advantage of site specificity, non-invasive and non-toxic application, require inexpensive equipment and can be given as repetitive treatment protocols.

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“…PTT is an effective method of achieving rapid elevated temperatures in targeted regions in the presence of NIR absorbing gold nanoparticles while limiting damage to normal structures. The efficacy of PTT induced moderate hyperthermia in several forms of combined therapy has been shown to be effective [34][35][36]. Experiments examining the effects of combined PTT + PCI treatment modalities are in progress.…”

Section: Combined Pci Mediated Chemotherapy and External Induced Mhtmentioning

confidence: 99%

Synergistic chemotherapy by combined moderate hyperthermia and photochemical internalization

Christie

Molina

Gonzales

et al. 2016

Biomed. Opt. Express

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Combination therapies of photochemical internalization (PCI) and moderate hyperthermia (MHT) were investigated in an in vitro system consisting of human and rat glioma spheroids. PCI using the amphiphilic photosensitizer, AlPcS2a and two anti cancer agents BLM or 5-FU were used. Spheroids were irradiated with λ = 670 nm laser light in an incubator at temperatures ranging from 37 to 44°C. For each temperature investigated, spheroids were divided into 4 groups: control, drug-only, photodynamic therapy (PDT), and PCI. PDT and PCI spheroids were exposed to radiant exposures ranging from 0.3 to 2.5 J cm −2 using an irradiance of 5 mW cm −2 . Toxicity was evaluated from spheroid growth kinetics. The combination of PCI and MHT resulted in significant increases in BLM efficacy at 44°C for both cell line derived spheroids compared to controls at 37°C over the range of radiant exposures examined. 5-FU PCI was ineffective for the human cell line at both 37 and 44°C. L. West, "Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance," Proc. Natl. Acad. Sci. U.S.A. 100(23), 13549-13554 (2003). 31. X. Huang, P. K. Jain, I. H. El-Sayed, and M. A. El-Sayed, "Determination of the minimum temperature required for selective photothermal destruction of cancer cells with the use of immunotargeted gold nanoparticles," Photochem. Photobiol. 82(2), 412-417 (2006). 32.

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Synergistic Effects of Cisplatin Chemotherapy and Gold Nanorod-Mediated Hyperthermia on Ovarian Cancer Cells and Tumors

Cited by 47 publications

References 65 publications

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

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

Enhancing the effects of chemotherapy by combined macrophage-mediated photothermal therapy (PTT) and photochemical internalization (PCI)

Synergistic chemotherapy by combined moderate hyperthermia and photochemical internalization

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