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Changes in plasma membrane damage inducing cell death after treatment with near-infrared photoimmunotherapy

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Title: Changes in plasma membrane damage inducing cell death after treatment with near-infrared photoimmunotherapy
Authors: Nakajima, Kohei Browse this author
Takakura, Hideo Browse this author
Shimizu, Yoichi Browse this author
Ogawa, Mikako Browse this author →KAKEN DB
Keywords: cell membrane damage
immunogenic cell death
near-infrared photoimmunotherapy
Issue Date: Sep-2018
Publisher: John Wiley & Sons
Journal Title: Cancer science
Volume: 109
Issue: 9
Start Page: 2889
End Page: 2896
Publisher DOI: 10.1111/cas.13713
Abstract: Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer phototherapy modality using an antibody conjugated to a photosensitizer, IRDye700DX. When the conjugate binds to the plasma membrane and is exposed to NIR light, NIR-PIT-treated cells undergo swelling, and target-selective necrotic/immunogenic cell death is induced. However, the cytotoxic mechanism of NIR-PIT has not been elucidated. In order to understand the mechanism, it is important to elucidate how the damage to the plasma membrane induced by NIR light irradiation changes over time. Thus, in the present study, we investigated the changes in plasma membrane permeability using ions and molecules of various sizes. Na+ flowed into cells immediately after NIR light irradiation, even when the function of transporters or channels was blocked. Subsequently, fluorescent molecules larger than Na+ entered the cells, but the damage was not large enough for dextran to pass through at early time points. To assess these phenomena quantitatively, membrane permeability was estimated using radiolabeled ions and molecules: (InCl3)-In-111, In-111-DTPA, and H-3-H2O, and comparable results were obtained. Although minute plasma membrane perforations usually do not induce cell death, our results suggest that the minute damage induced by NIR-PIT was irreversibly extended with time. In conclusion, minute plasma membrane damage is a trigger for the increase in plasma membrane permeability, cell swelling, and necrotic/immunogenic cell death in NIR-PIT. Our findings provide new insight into the cytotoxic mechanism of NIR-PIT.
Type: article
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 小川 美香子

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