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Photoinduced Ligand Release from a Silicon Phthalocyanine Dye Conjugated with Monoclonal Antibodies: A Mechanism of Cancer Cell Cytotoxicity after Near-Infrared Photoimmunotherapy

2018; American Chemical Society; Volume: 4; Issue: 11 Linguagem: Inglês

10.1021/acscentsci.8b00565

2374-7951

Kazuhide Sato, Kanta Ando, Shuhei Okuyama, Shiho Moriguchi, Tairo Ogura, Shinichiro Totoki, Hirofumi Hanaoka, Tadanobu Nagaya, Ryohei Kokawa, Hideo Takakura, Masayuki Nishimura, Yoshinori Hasegawa, Peter L. Choyke, Mikako Ogawa, Hisataka Kobayashi,

Porphyrin and Phthalocyanine Chemistry

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.