Electron Donors Rather Than Reactive Oxygen Species Needed for Therapeutic Photochemical Reaction of Near-Infrared Photoimmunotherapy,ACS Pharmacology & Translational Science

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Electron Donors Rather Than Reactive Oxygen Species Needed for Therapeutic Photochemical Reaction of Near-Infrared Photoimmunotherapy
ACS Pharmacology & Translational Science ( IF 4.9 ) Pub Date : 2021-09-17 , DOI: 10.1021/acsptsci.1c00184
Takuya Kato ₁ , Ryuhei Okada ₁ , Yuto Goto ₂ , Aki Furusawa ₁ , Fuyuki Inagaki ₁ , Hiroaki Wakiyama ₁ , Hideyuki Furumoto ₁ , Dagane Daar ₁ , Baris Turkbey ₁ , Peter L Choyke ₁ , Hideo Takakura ₂ , Osamu Inanami ₃ , Mikako Ogawa ₂ , Hisataka Kobayashi ₁

Affiliation

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.

中文翻译：

电子供体而不是近红外光免疫疗法的治疗性光化学反应所需的活性氧

近红外光免疫疗法 (NIR-PIT) 采用分子靶向抗体与与癌细胞结合的光吸收硅酞菁染料衍生物结合。在抗体-光吸收剂偶联物 (APC) 结合后应用 NIR 光导致染料上的配体释放，APC-抗原复合物的溶解度发生显着变化，并以高度选择性的方式对癌细胞造成快速、不可逆的细胞膜损伤，导致高度免疫原性的细胞死亡。临床上，该过程在活性氧 (ROS) 介导的治疗后导致水肿。基于 NIR-PIT 细胞毒性和水肿形成的化学和生物学机制，为了在不影响治疗效果的情况下最大限度地减少急性炎症性水肿，L-抗坏血酸钠（l -NaAA) 用于淬灭有害 ROS 并加速配体释放反应。l -NaAA 通过减少 NIR-PIT 后的 ROS 来抑制急性水肿，但不改变治疗效果。NIR-PIT 可以在l- NaAA 存在下安全地进行，不会产生不必要的 ROS 产生的副作用。

更新日期：2021-10-08

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