Genetically Encoded Immunophotosensitizer 4D5scFv-miniSOG is a Highly Selective Agent for Targeted Photokilling of Tumor Cells in<i> Vitro</i>

Миронова, К. Е.; Прошкина, Г. М.; Ryabova, A. V.; Stremovskiy, Oleg A.; Lukyanov, Sergey; Петров, Р. В.; Deyev, Sergey M.

doi:10.7150/thno.6715

Cited by 76 publications

(54 citation statements)

References 31 publications

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“…274 Another study employed genetically encoded immune-PS 4D5scFv-miniSOG to selectively recognize the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu), a receptor overexpressed in many human carcinomas. 283 The recombinant protein 4D5scFv-miniSOG exerted a highly specific photo-induced cytotoxic effect on HER2/neu-positive SK-BR-3 human breast adenocarcinoma cells (IC 50 = 160 nM). 283 However, blue light has limited propagation through the tissue and may hinder the wide applications of miniSOG in clinical practice.…”

Section: Genetically Encoded Photosensitizersmentioning

confidence: 99%

“…283 The recombinant protein 4D5scFv-miniSOG exerted a highly specific photo-induced cytotoxic effect on HER2/neu-positive SK-BR-3 human breast adenocarcinoma cells (IC 50 = 160 nM). 283 However, blue light has limited propagation through the tissue and may hinder the wide applications of miniSOG in clinical practice. In this regard, future studies might require light delivery systems to permit interstitial activation of miniSOG for in-depth PDT, as described in Section 2.…”

Section: Genetically Encoded Photosensitizersmentioning

confidence: 99%

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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: Genetically Encoded Photosensitizersmentioning

confidence: 99%

Section: Genetically Encoded Photosensitizersmentioning

confidence: 99%

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

et al. 2016

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“…CALI has also been used as a 'switch' in optogenetics because it can disrupt chromatin and proteins in a locus-specific manner, kill specific organelles or a single cell in vivo Lin et al, 2013). Moreover, CALI is beginning to be exploited in photodynamic therapy of cancer cells (Mironova et al, 2013;Ryumina et al, 2013;Shirmanova et al, 2013;Liao et al, 2014). Therefore, we anticipate that the portfolio of applications of CALI will further expand, and contribute to a series of remarkable biological findings and medical applications in the future.…”

Section: Discussionmentioning

confidence: 99%

Chromophore-assisted laser inactivation – towards a spatiotemporal–functional analysis of proteins, and the ablation of chromatin, organelle and cell function

Sano

Watanabe

Matsunaga

2014

Journal of Cell Science

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Chromophore-assisted laser or light inactivation (CALI) has been employed as a promising technique to achieve spatiotemporal knockdown or loss-of-function of target molecules in situ. CALI is performed using photosensitizers as generators of reactive oxygen species (ROS). There are two CALI approaches that use either transgenic tags with chemical photosensitizers, or genetically encoded fluorescent protein fusions. Using spatially restricted microscopy illumination, CALI can address questions regarding, for example, protein isoforms, subcellular localization or phase-specific analyses of multifunctional proteins that other knockdown approaches, such as RNA interference or treatment with chemicals, cannot. Furthermore, rescue experiments can clarify the phenotypic capabilities of CALI after the depletion of endogenous targets. CALI can also provide information about individual events that are involved in the function of a target protein and highlight them in multifactorial events. Beyond functional analysis of proteins, CALI of nuclear proteins can be performed to induce cell cycle arrest, chromatin-or locus-specific DNA damage. Even at organelle levelsuch as in mitochondria, the plasma membrane or lysosomes -CALI can trigger cell death. Moreover, CALI has emerged as an optogenetic tool to switch off signaling pathways, including the optical depletion of individual neurons. In this Commentary, we review recent applications of CALI and discuss the utility and effective use of CALI to address open questions in cell biology.

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“…MiniSOG localized to the mitochondria, plasma membrane, or chromatin was shown to mediate blue lightinduced death of mammalian cells in vitro (13). Also, externally added miniSOG (fused to an antibody or DARPin for cell typespecific targeting) possessed high phototoxicity against tumor cells in vitro (14,15). …”

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confidence: 99%

Lysosome-Associated MiniSOG as a Photosensitizer for Mammalian Cells

et al. 2016

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Genetically encoded photosensitizers represent a promising optogenetic tool for the induction of light-controlled oxidative stress strictly localized to a selected intracellular compartment. Here we tested the phototoxic effects of the flavin-containing phototoxic protein miniSOG targeted to the cytoplasmic surfaces of late endosomes and lysosomes by fusion with Rab7. In HeLa Kyoto cells stably expressing miniSOG-Rab7, we demonstrated a high level of cell death upon blue-light illumination. Pepstatin A completely abolished phototoxicity of miniSOG-Rab7, showing a key role for cathepsin D in this model. Using a far-red fluorescence sensor for caspase-3, we observed caspase-3 activation during miniSOG-Rab7–mediated cell death. We conclude that upon illumination, miniSOG-Rab7 induces lysosomal membrane permeabilization (LMP) and leakage of cathepsins into the cytosol, resulting in caspase-dependent apoptosis.

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Genetically Encoded Immunophotosensitizer 4D5scFv-miniSOG is a Highly Selective Agent for Targeted Photokilling of Tumor Cells in Vitro

Cited by 76 publications

References 31 publications

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

Chromophore-assisted laser inactivation – towards a spatiotemporal–functional analysis of proteins, and the ablation of chromatin, organelle and cell function

Lysosome-Associated MiniSOG as a Photosensitizer for Mammalian Cells

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