Changes in plasma membrane damage inducing cell death after treatment with near‐infrared photoimmunotherapy. Issue 9 (14th July 2018)

• Record Type: Journal Article
• Authors: Nakajima, Kohei; Takakura, Hideo; Shimizu, Yoichi; Ogawa, Mikako
• Is Part Of: Cancer science. Volume 109:Issue 9(2018)
• Page Start: 2889
• Page End: 2896
• Publication Date: 2018-07-14
• Subjects: cell membrane damage -- immunogenic cell death -- near‐infrared photoimmunotherapy -- photosensitizer -- phototherapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13713
• Languages: English
• ISSNs: 1347-9032

Abstract

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: 111 InCl3, 111 In‐DTPA, and 3 H‐H2 O, 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. Abstract : In the present study, the cytotoxic mechanism of photoimmunotherapy was investigated. As a result, we found that minute irreversible damage of the cell plasma membrane was produced after near‐infrared light irradiation. This damage was not recovered in the usual biological process, but it was expanded to cause fatal cell death.