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- Title
Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin.
- Authors
Nishinaga, Yuko; Sato, Kazuhide; Yasui, Hirotoshi; Taki, Shunichi; Takahashi, Kazuomi; Shimizu, Misae; Endo, Rena; Koike, Chiaki; Kuramoto, Noriko; Nakamura, Shota; Fukui, Takayuki; Yukawa, Hiroshi; Baba, Yoshinobu; K. Kaneko, Mika; Chen-Yoshikawa, Toyofumi F.; Kobayashi, Hisataka; Kato, Yukinari; Hasegawa, Yoshinori
- 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.
- Subjects
MESOTHELIOMA; PHOTOTHERAPY; ASBESTOS; CANCER treatment; CELL lines; IMMUNOGLOBULINS
- Publication
Cells (2073-4409), 2020, Vol 9, Issue 4, p1019
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells9041019