Evaluation of Firefly Luciferase Bioluminescence Mediated Photodynamic Toxicity in Cancer Cells

Schipper, Meike L.; Patel, Manishkumar; Gambhir, Sanjiv S.

doi:10.1007/s11307-006-0048-1

Cited by 32 publications

(42 citation statements)

References 26 publications

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“…114, 115 Dated back to 1994, a similar concept of bioluminescence-based PDT was reported by Carpenter et al, who investigated its potential using Photinus pyralis luciferin/luciferase system as bioluminescence light source. 116117, 118 Rao et al developed an eight-mutation variant of Rluc, denoted as Rluc8, which is more stable in serum and has improved catalytic efficiency compared with the wild-type protein, suitable for BRET imaging and bio-sensing in vivo . 61 …”

Section: Depth Penetrationmentioning

confidence: 99%

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

et al. 2016

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Reactive oxygen species (ROS)-mediated mechanism is the major cause underlying the efficacy of photodynamic therapy (PDT). The PDT procedure is based on the cascade of synergistic effects between light, photosensitizer (PS) and oxygen, which greatly favor the spatiotemporal control of the treatment. This procedure has also evoked several unresolved challenges at different levels including (i) limited penetration depth of light restricts traditional PDT to only superficial tumours; (ii) oxygen reliance deprives PDT treatment of hypoxic tumours; (iii) light could complicate the phototherapeutic outcomes due to the concurrent heat generation; (iv) specific delivery of PSs to sub-cellular organelles for exerting effective toxicity remains an issue; and (v) side effects by undesirable white-light activation and self-catalysation of traditional PSs. Recent advances in nanotechnology and nanomedicine have provided new opportunities to develop ROS-generating systems through photodynamic or non-photodynamic procedures while tackling the challenges of current PDT approaches. In this review, we summarize the current status and discuss the possible opportunities of ROS generation for cancer therapy. We hope this review will spur pre-clinical research and clinical practice for ROS-mediated tumour treatment.

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Section: Depth Penetrationmentioning

confidence: 99%

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

et al. 2016

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“…Later, Theodossiou et al investigated the capacity of the oxyluciferin to activate the PS rose Bengal in vitro and induce cell death in murine fibroblasts 55. Although Schipper et al has more recently contested these results 56, the viability of cells transfected with the luciferase gene was reduced to (11±12)% when treated with 10 nM Rose Bengal. Schipper et al strongly questioned the efficiency of the bioluminescence-activated PDT by showing that the light dose emitted by the bioluminescence probe (on the order of 10 -9 mW.cm -2 ) was significantly lower than the doses typically employed in clinical trials for laser activated-PDT (~ 50 mW.cm -2 ) 56.…”

Section: Forward Looking Methodologies For Deep Tissue Pdtmentioning

confidence: 99%

“…Although Schipper et al has more recently contested these results 56, the viability of cells transfected with the luciferase gene was reduced to (11±12)% when treated with 10 nM Rose Bengal. Schipper et al strongly questioned the efficiency of the bioluminescence-activated PDT by showing that the light dose emitted by the bioluminescence probe (on the order of 10 -9 mW.cm -2 ) was significantly lower than the doses typically employed in clinical trials for laser activated-PDT (~ 50 mW.cm -2 ) 56. Besides this fundamental concern, several follow up studies demonstrated improved killing stemming from either bio- or chemi-luminescence activated PDT, highlighting our limited understanding of the mechanisms underlying these energy transfers since ostensibly the reduced energy densities emitted by the luminescent probes can still activate PS and impart cytotoxicity.…”

Section: Forward Looking Methodologies For Deep Tissue Pdtmentioning

confidence: 99%

Beyond the Barriers of Light Penetration: Strategies, Perspectives and Possibilities for Photodynamic Therapy

Mallidi¹,

Anbil

Bulin³

et al. 2016

Theranostics

322

237

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Photodynamic therapy (PDT) is a photochemistry based treatment modality that involves the generation of cytotoxic species through the interactions of a photosensitizer molecule with light irradiation of an appropriate wavelength. PDT is an approved therapeutic modality for several cancers globally and in several cases has proved to be effective where traditional treatments have failed. The key parameters that determine PDT efficacy are 1. the photosensitizer (nature of the molecules, selectivity, and macroscopic and microscopic localization etc.), 2. light application (wavelength, fluence, fluence rate, irradiation regimes etc.) and 3. the microenvironment (vascularity, hypoxic regions, stromal tissue density, molecular heterogeneity etc.). Over the years, several groups aimed to monitor and manipulate the components of these critical parameters to improve the effectiveness of PDT treatments. However, PDT is still misconstrued to be a surface treatment primarily due to the limited depths of light penetration. In this review, we present the recent advances, strategies and perspectives in PDT approaches, particularly in cancer treatment, that focus on increasing the 'damage zone' beyond the reach of light in the body. This is enabled by a spectrum of approaches that range from innovative photosensitizer excitation strategies, increased specificity of phototoxicity, and biomodulatory approaches that amplify the biotherapeutic effects induced by photodynamic action. Along with the increasing depth of understanding of the underlying physical, chemical and physiological mechanisms, it is anticipated that with the convergence of these strategies, the clinical utility of PDT will be expanded to a powerful modality in the armamentarium for the management of cancer.

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“…Similarly conflicting results were obtained on examination of luciferase bioluminescence in the presence of photosensitizing agents. Luciferase activity was reported to be sufficient to drive photodynamic cytotoxicity in NIH 3T3 cells [18], but this finding was not generalizable to other cells [19]. …”

Section: Introductionmentioning

confidence: 99%

Luciferase does not alter metabolism in cancer cells

et al. 2014

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Luciferase transfected cell lines are used extensively for cancer models, revealing valuable biological information about disease mechanisms. However, these genetically encoded reporters, while useful for monitoring tumor response in cancer models, can impact cell metabolism. Indeed firefly luciferase and fatty acyl-CoA synthetases differ by a single amino acid, raising the possibility that luciferase activity might alter metabolism and introduce experimental artifacts. Therefore knowledge of the metabolic response to luciferase transfection is of significant importance, especially given the thousands of research studies using luciferase as an in vivo bioluminescence imaging (BLI) reporter. Untargeted metabolomics experiments were performed to examine three different types of lymphoblastic leukemia cell lines (Ramos, Raji and SUP T1) commonly used in cancer research, each were analyzed with and without vector transduction. The Raji model was also tested under perturbed starvation conditions to examine potential luciferase-mediated stress responses. The results showed that no significant metabolic differences were observed between parental and luciferase transduced cells for each cell line, and that luciferase overexpression does not alter cell metabolism under basal or perturbed conditions.

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Evaluation of Firefly Luciferase Bioluminescence Mediated Photodynamic Toxicity in Cancer Cells

Abstract: Contesting recent reports, fLuc bioluminescence does not generate sufficient photons to induce Rose Bengal or hypericin photodynamic toxicity in a range of malignant and nonmalignant cell lines, and is not suitable as a generalizable approach to antineoplastic therapy.

Cited by 32 publications

References 26 publications

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

Beyond the Barriers of Light Penetration: Strategies, Perspectives and Possibilities for Photodynamic Therapy

Luciferase does not alter metabolism in cancer cells

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