Electron Donors Rather Than Reactive Oxygen Species Needed for Therapeutic Photochemical Reaction of Near-Infrared Photoimmunotherapy.
Takuya KatoRyuhei OkadaYuto GotoAki FurusawaFuyuki F InagakiHiroaki WakiyamaHideyuki FurumotoDagane DaarBaris TurkbeyPeter L ChoykeHideo TakakuraOsamu InanamiMikako OgawaHisataka KobayashiPublished in: ACS pharmacology & translational science (2021)
Near-infrared photoimmunotherapy (NIR-PIT) employs molecularly targeted antibodies conjugated with a photoabsorbing silicon-phthalocyanine dye derivative which binds to cancer cells. Application of NIR light following binding of the antibody-photoabsorber conjugates (APCs) results in ligand release on the dye, dramatic changes in solubility of the APC-antigen complex, and rapid, irreversible cell membrane damage of cancer cells in a highly selective manner, resulting in a highly immunogenic cell death. Clinically, this process results in edema after treatment mediated by reactive oxygen species (ROS). Based on the chemical and biological mechanism of NIR-PIT cytotoxicity and edema formation, in order to minimize acute inflammatory edema without compromising therapeutic effects, l-sodium ascorbate (l-NaAA) was administered to quench harmful ROS and accelerate the ligand release reaction. l-NaAA suppressed acute edema by reducing ROS after NIR-PIT yet did not alter the therapeutic effects. NIR-PIT could be performed safely under existence of l-NaAA without side effects caused by unnecessary ROS production.
Keyphrases
- reactive oxygen species
- photodynamic therapy
- cell death
- fluorescence imaging
- drug release
- fluorescent probe
- liver failure
- dna damage
- respiratory failure
- drug induced
- cancer therapy
- aortic dissection
- drug delivery
- intensive care unit
- water soluble
- sensitive detection
- mechanical ventilation
- binding protein
- solar cells
- aqueous solution