Research Papers:

Dynamic changes in the cell membrane on three dimensional low coherent quantitative phase microscopy (3D LC-QPM) after treatment with the near infrared photoimmunotherapy

Fusa Ogata, Tadanobu Nagaya, Shuhei Okuyama, Yasuhiro Maruoka, Peter L. Choyke, Toyohiko Yamauchi and Hisataka Kobayashi _

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Oncotarget. 2017; 8:104295-104302. https://doi.org/10.18632/oncotarget.22223

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Fusa Ogata1, Tadanobu Nagaya1, Shuhei Okuyama1, Yasuhiro Maruoka1, Peter L. Choyke1, Toyohiko Yamauchi2 and Hisataka Kobayashi1

1Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States of America

2Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu 434-8601, Japan

Correspondence to:

Hisataka Kobayashi, email: [email protected]

Keywords: near infrared photoimmunotherapy; cell membrane damage; live cell imaging; immunogenic cell death

Received: July 14, 2017     Accepted: October 13, 2017     Published: November 01, 2017


Near infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer therapy that relies on the binding of a near-infrared antibody photoabsorber conjugate (APC) to a cancer cell. Subsequent exposure to NIR light selectively induces rapid necrotic cell death on target-expressing cells with minimal off-target effects. When treated with NIR-PIT, targeted cells become swollen, develop blebs and burst within minutes of light exposure. Detailed spatial and temporal morphological changes of the cellular membrane of targeted cells treated with NIR-PIT have not been fully explored with state-of-the-art microscopic methods. In this study, we investigated the morphologic and kinetic effects of PIT on two types of cells, a spindle-shaped 3T3/Her cell and a spheric-shaped MDA-MB468 cell, after NIR-PIT using three-dimensional low-coherent quantitative phase microscopy (3D LC-QPM). Adhesive cells treated with NIR-PIT demonstrated region-specific cell membrane rupture occurring first on the distal free edge of the cell near the site of adhesion, in a process that was independent of cell shape. The results show that the peripheral portions of the cell membrane near the site of adhesion are particularly vulnerable to the effects of NIR-PIT, likely because these sites exhibit higher baseline surface tension.

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