Photoinduced Ligand Release from a Silicon Phthalocyanine Dye Conjugated with Monoclonal Antibodies: A Mechanism of Cancer Cell Cytotoxicity after Near-Infrared Photoimmunotherapy.
作者信息
Sato Kazuhide, Ando Kanta, Okuyama Shuhei, Moriguchi Shiho, Ogura Tairo, Totoki Shinichiro, Hanaoka Hirofumi, Nagaya Tadanobu, Kokawa Ryohei, Takakura Hideo, Nishimura Masayuki, Hasegawa Yoshinori, Choyke Peter L, Ogawa Mikako, Kobayashi Hisataka
机构信息
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1088, United States.
Institute for Advanced Research, Nagoya University, Nagoya, Aichi 464-0814, Japan.
出版信息
ACS Cent Sci. 2018 Nov 28;4(11):1559-1569. doi: 10.1021/acscentsci.8b00565. Epub 2018 Nov 6.
Photochemical reactions can dramatically alter physical characteristics of reacted molecules. In this study, we demonstrate that near-infrared (NIR) light induces an axial ligand-releasing reaction, which dramatically alters hydrophilicity of a silicon phthalocyanine derivative (IR700) dye leading to a change in the shape of the conjugate and its propensity to aggregate in aqueous solution. This photochemical reaction is proposed as a major mechanism of cell death induced by NIR photoimmunotherapy (NIR-PIT), which was recently developed as a molecularly targeted cancer therapy. Once the antibody-IR700 conjugate is bound to its target, activation by NIR light causes physical changes in the shape of antibody antigen complexes that are thought to induce physical stress within the cellular membrane leading to increases in transmembrane water flow that eventually lead to cell bursting and necrotic cell death.