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

2018 ◽  
Vol 4 (11) ◽  
pp. 1559-1569 ◽  
Author(s):  
Kazuhide Sato ◽  
Kanta Ando ◽  
Shuhei Okuyama ◽  
Shiho Moriguchi ◽  
Tairo Ogura ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cancer Cell ◽  
Near Infrared ◽  
Cell Cytotoxicity ◽  
Silicon Phthalocyanine

scholarly journals Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates

2014 ◽  
Vol 111 (10) ◽  
pp. E933-E942 ◽  
Author(s):  
Bryan Q. Spring ◽  
Adnan O. Abu-Yousif ◽  
Akilan Palanisami ◽  
Imran Rizvi ◽  
Xiang Zheng ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Near Infrared ◽  
Dual Function ◽  
Imaging Method ◽  
Drug Resistant ◽  
Micrometastatic Disease ◽  
Selective Treatment ◽  
Cell Internalization ◽  
Occult Disease

Drug-resistant micrometastases that escape standard therapies often go undetected until the emergence of lethal recurrent disease. Here, we show that it is possible to treat microscopic tumors selectively using an activatable immunoconjugate. The immunoconjugate is composed of self-quenching, near-infrared chromophores loaded onto a cancer cell-targeting antibody. Chromophore phototoxicity and fluorescence are activated by lysosomal proteolysis, and light, after cancer cell internalization, enabling tumor-confined photocytotoxicity and resolution of individual micrometastases. This unique approach not only introduces a therapeutic strategy to help destroy residual drug-resistant cells but also provides a sensitive imaging method to monitor micrometastatic disease in common sites of recurrence. Using fluorescence microendoscopy to monitor immunoconjugate activation and micrometastatic disease, we demonstrate these concepts of “tumor-targeted, activatable photoimmunotherapy” in a mouse model of peritoneal carcinomatosis. By introducing targeted activation to enhance tumor selectively in complex anatomical sites, this study offers prospects for catching early recurrent micrometastases and for treating occult disease.

Axially-substituted silicon phthalocyanine payloads for antibody-drug conjugates

Synlett ◽  
2021 ◽  
Author(s):  
Kazuki Takahashi ◽  
Akira Sugiyama ◽  
Kei Ohkubo ◽  
Toshifumi Tatsumi ◽  
Tatsuhiko Kodama ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Antibody Drug Conjugate ◽  
Antibody Drug Conjugates ◽  
Drug Conjugate ◽  
Drug Conjugates ◽  
Antibody Drug ◽  
Silicon Phthalocyanine

IR700, a silicon phthalocyanine (SiPc) photosensitizer, is an antibody-drug conjugate payload used clinically. It is, however, the sole SiPc payload to date, possibly due to the difficulty of its synthesis, resulting from its asymmetric phathalocyanine skeleton. Here we report a new axially-substituted SiPc payload with easier synthesis. Trastuzumab conjugated with the SiPc showed light- and antigen-dependent cytotoxicity in HER2-overexpressed cancer cell lines.

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