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Zinc-Substituted Hemoglobin–Albumin Cluster as a Porphyrin-Carrier for Enhanced Photodynamic Therapy
Chemistry - An Asian Journal ( IF 4.1 ) Pub Date : 2024-04-17 , DOI: 10.1002/asia.202400257
Taiga Yamada 1 , Maho Katsumi 2 , Kota Ishii 2 , Teruyuki Komatsu 2
Affiliation  

Apohemoprotein is focused on the field of theranostics, serving as a porphyrin carrier. Hemoglobin (Hb) consists of α2β2 tetramer with iron(II)-protoporphyrin IX (heme) bound to each globin. However, heme-removed Hb (apoHb) causes dissociation at αβ interfaces and aggregation under physiological conditions. We synthesized a stable apoHb derivative comprising intramolecular-crosslinked apoHb (apoXHb) and human serum albumin (HSA), apoXHb-HSA3. ApoXHb-HSA3 engendered no aggregates in the physiological solutions. Moreover, apoXHb-HSA3 was reconstituted with zinc(II)-protoporphyrin IX (ZnP), generating ZnXHb-HSA3, a potent photosensitizer for photodynamic therapy (PDT). The photophysical properties of ZnXHb-HSA3 were identical to those of zinc-substituted XHb (ZnXHb). Cellular uptake behavior was evaluated using various cancer cell lines. ZnXHb-HSA3 released ZnP around the cells, and the free ZnP penetrated cell membranes. In contrast, protein units were not observed within the cells. ZnXHb-HSA3 showed no cytotoxicity under dark conditions and demonstrated superior PDT activity in comparison to naked ZnXHb. ZnXHb-HSA3 acts as an innovative porphyrin carrier for enhanced PDT.

中文翻译:

锌取代的血红蛋白-白蛋白簇作为卟啉载体用于增强光动力治疗

阿朴血红素蛋白专注于治疗诊断学领域,作为卟啉载体。血红蛋白 (Hb) 由 α 2 β 2四聚体组成,每个球蛋白均结合有铁 (II)-原卟啉 IX(血红素)。然而,去除血红素的 Hb (apoHb) 会导致 αβ 界面解离并在生理条件下聚集。我们合成了包含分子内交联的apoHb (apoXHb) 和人血清白蛋白(HSA) 的稳定apoHb 衍生物,apoXHb-HSA 3。 ApoXHb-HSA 3在生理溶液中不产生聚集体。此外,apoXHb-HSA 3用锌(II)-原卟啉IX (ZnP) 重构,生成ZnXHb-HSA 3,这是一种用于光动力疗法(PDT)的有效光敏剂。 ZnXHb-HSA 3的光物理性质与锌取代的XHb (ZnXHb) 相同。使用各种癌细胞系评估细胞摄取行为。 ZnXHb-HSA 3在细胞周围释放ZnP,并且游离的ZnP穿透细胞膜。相反,在细胞内没有观察到蛋白质单位。 ZnXHb-HSA 3在黑暗条件下没有表现出细胞毒性,并且与裸露的 ZnXHb 相比表现出优异的 PDT 活性。 ZnXHb-HSA 3作为一种创新的卟啉载体,可增强 PDT。
更新日期:2024-04-17
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