Catalase-Albumin Cluster Incorporating Protoporphyrin IX: O2 Generating Photosensitizer for Enhanced Photodynamic Therapy
Catalase-Albumin Cluster Incorporating Protoporphyrin IX: O2 Generating Photosensitizer for Enhanced Photodynamic Therapy
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结合原卟啉 IX 的过氧化氢酶-白蛋白簇：用于增强光动力治疗的 O2 生成光敏剂
DOI：
10.1039/d2ma00242f
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
T. Komatsu
中科院分区：
文献类型：
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作者：
T. Yamada;M. Katsumi;Y. Yagisawa;M. Ichihara;T. Komatsu
光动力疗法（PDT）是一种利用光照射产生的活性氧（ROS）的非侵入性癌症治疗方法。激发态光敏剂通过电子转移反应（I型）产生活性自由基（例如O2 stec-和OH stec），而激发三重态光敏剂通过直接能量转移到分子O2（II型）产生单线态O2（1 O2）。本报告描述了基于血红素的光敏剂的合成和PDT活性与O2产生能力的结合。过氧化氢酶（Cat）与人血清白蛋白（HSA）的共价包裹产生核-壳结构的蛋白质簇Cat-HSA 5，其中平均5个HSA分子结合到Cat中心。Cat-HSA 5保留了过氧化氢（H2 O2）还原反应的高酶活性。随后，将原卟啉IX（PP）掺入单个HSA单元中产生Cat-（HSA-PP）5簇。Cat-（HSA-PP）5的1 O2生成能力与HSA-PP复合物相当。使用HeLa细胞评价光照射的细胞毒性。Cat-（HSA-PP）5表现出比HSA-PP复合物更高的PDT活性。Cat核心在细胞中有效地激发内源性H2 O2向O2的转化，以促进大量的1 O2形成。Cat-（HSA-PP）5是一种独特的双功能血红素蛋白簇（O2生成和光敏化），可以实现增强的PDT。
Photodynamic therapy (PDT) is a non-invasive cancer treatment using reactive oxygen species (ROS) generated by light irradiation. An excited state photosensitizer produces active radicals (e.g. O2˙− and OH˙) by electron transfer reactions (type I), while an excited triplet state photosensitizer generates singlet O2 (1O2) by direct energy transfer to molecular O2 (type II). This report describes the synthesis and PDT activity of the hemoprotein-based photosensitizer combined with O2 production capability. Covalent wrapping of a catalase (Cat) with human serum albumins (HSAs) yielded the core–shell structured protein cluster Cat-HSA5, in which an average of five HSA molecules are bound to the Cat center. Cat-HSA5 retained the high enzymatic activity of the hydrogen peroxide (H2O2) disproportionation reaction. Subsequently, the incorporation of protoporphyrin IX (PP) into an individual HSA unit resulted in a Cat-(HSA-PP)5 cluster. The 1O2 generation ability of Cat-(HSA-PP)5 was equivalent to that of the HSA–PP complex. Cytotoxicity with light irradiation was evaluated using HeLa cells. Cat-(HSA-PP)5 demonstrated higher PDT activity than the HSA–PP complex. The Cat core provoked conversion of endogenous H2O2 to O2 efficiently in the cells to facilitate 1O2 formation in large amounts. Cat-(HSA-PP)5 is a unique dual functional hemoprotein cluster (O2 generation and photosensitization) that can achieve enhanced PDT.