Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin

Yuko Nishinaga, Kazuhide Sato, Hirotoshi Yasui, Shunichi Taki, Kazuomi Takahashi, Misae Shimizu, Rena Endo, Chiaki Koike, Noriko Kuramoto, Shota Nakamura, Takayuki Fukui, Hiroshi Yukawa, Yoshinobu Baba, Mika K Kaneko, Toyofumi F. Chen-Yoshikawa, Hisataka Kobayashi, Yukinari Kato, Yoshinori Hasegawa

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalCells
Volume9
Issue number4
DOIs
Publication statusPublished - 2020 Apr 20

Keywords

  • malignant pleural mesothelioma
  • near-infrared photoimmunotherapy
  • podoplanin (PDPN)

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin'. Together they form a unique fingerprint.

Cite this