Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin
by
Yuko Nishinaga 1,†, Kazuhide Sato 1,2,3,*,†, Hirotoshi Yasui 1, Shunichi Taki 1, Kazuomi Takahashi 1, Misae Shimizu 1,2, Rena Endo 1,2, Chiaki Koike 1,2, Noriko Kuramoto 2, Shota Nakamura 4, Takayuki Fukui 4, Hiroshi Yukawa 2,5,6
, Yoshinobu Baba 5,6, Mika K. Kaneko 7, Toyofumi F. Chen-Yoshikawa 4, Hisataka Kobayashi 8, Yukinari Kato 7,9 and Yoshinori Hasegawa 10
Yuko Nishinaga 1,†, Kazuhide Sato 1,2,3,*,†, Hirotoshi Yasui 1, Shunichi Taki 1, Kazuomi Takahashi 1, Misae Shimizu 1,2, Rena Endo 1,2, Chiaki Koike 1,2, Noriko Kuramoto 2, Shota Nakamura 4, Takayuki Fukui 4, Hiroshi Yukawa 2,5,6, Yoshinobu Baba 5,6, Mika K. Kaneko 7, Toyofumi F. Chen-Yoshikawa 4, Hisataka Kobayashi 8, Yukinari Kato 7,9 and Yoshinori Hasegawa 10
1
Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
2
B3-Unit, Advanced Analytical and Diagnostic Imaging Center (AADIC)/Medical Engineering Unit (MEU), Nagoya University Institute for Advanced Research, Nagoya 466-8550, Japan
3
Nagoya University Institute for Advanced Research, S-YLC, Nagoya 464-8601, Japan
4
Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
5
Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Nagoya 464-8601, Japan
6
Department of Biomolecular Engineering, Nagoya University Graduate School of Engineering, Nagoya 464-8601, Japan
7
Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
8
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1088, USA
9
New Industry Creation Hatchery Center, Tohoku University, Sendai 980-8575, Japan
10
National Hospital Organization, Nagoya Medical Center, Nagoya 460-0001, Japan
*
Author to whom correspondence should be addressed.
†
These authors equally contributed to this work.
Cells 2020, 9(4), 1019; https://doi.org/10.3390/cells9041019
Received: 23 March 2020 / Revised: 15 April 2020 / Accepted: 16 April 2020 / Published: 20 April 2020
(This article belongs to the Special Issue Structure and Function of Podoplanin (PDPN) in Disease)
Malignant pleural mesothelioma (MPM) has extremely limited treatment despite a poor prognosis. Moreover, molecular targeted therapy for MPM has not yet been implemented; thus, a new targeted therapy is highly desirable. Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer therapy that combines the specificity of antibodies for targeting tumors with toxicity induced by the photoabsorber after exposure to NIR-light. In this study, we developed a new phototherapy targeting podoplanin (PDPN) for MPM with the use of both NIR-PIT and an anti-PDPN antibody, NZ-1. An antibody–photosensitizer conjugate consisting of NZ-1 and phthalocyanine dye was synthesized. In vitro NIR-PIT-induced cytotoxicity was measured with both dead cell staining and luciferase activity on various MPM cell lines. In vivo NIR-PIT was examined in both the flank tumor and orthotopic mouse model with in vivo real-time imaging. In vitro NIR-PIT-induced cytotoxicity was NIR-light dose dependent. In vivo NIR-PIT led to significant reduction in both tumor volume and luciferase activity in a flank model (p < 0.05, NIR-PIT group versus NZ-1-IR700 group). The PDPN-targeted NIR-PIT resulted in a significant antitumor effect in an MPM orthotopic mouse model (p < 0.05, NIR-PIT group versus NZ-1-IR700 group). This study suggests that PDPN-targeted NIR-PIT could be a new promising treatment for MPM.
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MDPI and ACS Style
Nishinaga, Y.; Sato, K.; Yasui, H.; Taki, S.; Takahashi, K.; Shimizu, M.; Endo, R.; Koike, C.; Kuramoto, N.; Nakamura, S.; Fukui, T.; Yukawa, H.; Baba, Y.; K. Kaneko, M.; Chen-Yoshikawa, T.F.; Kobayashi, H.; Kato, Y.; Hasegawa, Y. Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin. Cells 2020, 9, 1019.
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