Alterations of filopodia by near infrared photoimmunotherapy: evaluation with 3D low-coherent quantitative phase microscopy.

Yuko Nakamura,Shuhei Okuyama,Kazuhide Sato,Toshiko Harada,Peter L Choyke,Hisataka Kobayashi,Tadanobu Nagaya,Toyohiko Yamauchi

doi:10.1364/boe.7.002738

Abstract

Filopodia are highly organized cellular membrane structures that facilitate intercellular communication. Near infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that causes necrotic cell death. Three-dimensional low-coherent quantitative phase microscopy (3D LC-QPM) is based on a newly established low-coherent interference microscope designed to obtain serial topographic images of the cellular membrane. Herein, we report rapid involution of filopodia after NIR-PIT using 3D LC-QPM. For 3T3/HER2 cells, the number of filopodia decreased immediately after treatment with significant differences. Volume and relative height of 3T3/HER2 cells increased immediately after NIR light exposure, but significant differences were not observed. Thus, disappearance of filopodia, evaluated by 3D LC-QPM, is an early indicator of cell membrane damage after NIR-PIT.

Highlights

Near infrared photoimmunotherapy (NIR-PIT) is a new target-cell specific cancer treatment that employs an antibody-photoabsorber conjugate (APC) followed by NIR light exposure [1]
In the NIR-PIT group the number of filopodia decreased after NIR light exposure with a significant difference at all time points (p = 0.015 at 5 min,
In the NIR-PIT group the visual score of filopodia decreased after NIR light exposure with significant differences at all time point (p = 0.01 at 5, 10 and 15 min after NIR-light exposure) (Fig. 3 and Visualization 3)

Summary

Introduction

Near infrared photoimmunotherapy (NIR-PIT) is a new target-cell specific cancer treatment that employs an antibody-photoabsorber conjugate (APC) followed by NIR light exposure [1]. An APC consists of a cancer cell-specific monoclonal antibody (mAb) covalently conjugated to a photoabsorber, IRDye700DX (IR700), which is a silica-phthalocyanine derivative. NIR light exposure at 690 nm induces nearly immediate cell necrosis characterized by severe damage to the cell membrane. This mechanism of cell death stands in contrast to traditional photodynamic therapy in which a lipid soluble porphyrin derivative enters the cell and causes damage to the mitochondria resulting in an apoptotic cell death [2,3,4,5]. NIR-PIT induces nearly immediate necrotic cell death rather than apoptotic cell death which is induced by most other cancer therapies [6,7,8]

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Conclusion