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

被引：201

作者：

Sato, Kazuhide ^{[1
,2
,3
]}

Ando, Kanta ^{[4
]}

Okuyama, Shuhei ^{[1
,5
]}

Moriguchi, Shiho ^{[5
]}

Ogura, Tairo ^{[5
]}

Totoki, Shinichiro ^{[5
]}

Hanaoka, Hirofumi ^{[1
]}

Nagaya, Tadanobu ^{[1
]}

Kokawa, Ryohei ^{[5
]}

Takakura, Hideo ^{[4
]}

Nishimura, Masayuki ^{[5
]}

Hasegawa, Yoshinori ^{[3
]}

Choyke, Peter L. ^{[1
]}

Ogawa, Mikako ^{[4
]}

Kobayashi, Hisataka ^{[1
]}

机构：

[1] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[2] Nagoya Univ, Inst Adv Res, Nagoya, Aichi 4640814, Japan

[3] Nagoya Univ, Grad Sch Med, Dept Resp Med, Nagoya, Aichi 4668550, Japan

[4] Hokkaido Univ, Grad Sch Pharmaceut Sci, Lab Bioanal & Mol Imaging, Sapporo, Hokkaido 0600812, Japan

[5] Shimadzu Co Ltd, Kyoto 6048511, Japan

来源：

ACS CENTRAL SCIENCE | 2018年 / 4卷 / 11期

基金：

日本科学技术振兴机构; 美国国家卫生研究院;

关键词：

PHOTODYNAMIC THERAPY; IN-VIVO; ELIMINATION;

D O I：

10.1021/acscentsci.8b00565

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：1559 / 1569

页数：11

共 24 条

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