Year-end Sale % OFF 
Abstract
Near-infrared photoimmunotherapy (NIR-PIT) is a novel phototherapy for the treatment of cancer that uses NIR light and conjugates of antibody-IR700, a silicon phthalocyanine photosensitizer. A key feature of NIR-PIT is light-induced axial ligand cleavage of IR700, which finally causes cytotoxicity. Here, we focused on protonation of the axial ligand on the IR700 anion radical during the photochemical process. The Gibbs energy in the protonation reaction of IR700 derivatives with different axial ligands was calculated. These calculations suggested the order of the cleavage efficiency corresponds to the basicity of the axial ligand (i.e. alkoxy > siloxy (IR700) > phenoxy > oxycarbonyl), which was confirmed by the photoirradiation experiments with synthesized compounds. Thus, axial ligand cleavage is significantly dependent on the basicity of the axial ligand. Our findings suggest that PIT reagent with an IR700 derivative bearing alkoxy group would show better efficacy than IR700.
Highlights
IRDye700DX (IR700) is a silicon phthalocyanine (SiPc) derivative that absorbs near-infrared (NIR) light and has been used as a fluorescent imaging reagent and as a photosensitizer for NIR photoimmunotherapy (NIR-PIT) (Fig. 1a).[1,2] In NIR2PIT, IR700-antibody conjugate and NIR light are used to treat cancer
Because the cytotoxicity is induced only when the conjugate is bound to the cell membrane and irradiated with NIR light, NIR-PIT can kill cancer cells
We reported that in the presence of an electron donor under hypoxic conditions, the axial ligand of the IR700 derivative cleaves at pH 7.0, while at pH 11.0 no cleavage of the axial ligand occurs despite the generation of an anion radical.[9]
Summary
PIT, IR700-antibody conjugate and NIR light are used to treat cancer. Because the cytotoxicity is induced only when the conjugate is bound to the cell membrane and irradiated with NIR light, NIR-PIT can kill cancer cells. Various cancer antigens, such as epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), have been targeted. PIT has shown efficacy against gastric,[3,4] lung,[5] prostate,[6] and breast[7] cancers. Successful first-in-human phase I and II studies in patients with unresectable locally advanced head and neck cancer were completed (NCT02422979). Cetuximab-IR700, a PIT conjugate for EGFR, was approved in Japan. These studies suggest PIT will be a valuable new form of cancer treatment
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of Photochemistry and Photobiology A: Chemistry
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
