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用于缺氧细胞析氧光动力治疗的载酶锰卟啉金属有机纳米框架

Enzyme-loaded manganese-porphyrin metal-organic nanoframeworks for oxygen-evolving photodynamic therapy of hypoxic cells.

作者信息

Qiao Yang, Tang Xiaowan, Qiuju Xu, Zhang Guangwen

机构信息

Department of Hematology and Oncology, Wenzhou Medical University affiliated Huangyan Hospital, The First People's Hospital of Taizhou, People's Republic of China.

The Third Affiliated Hospital of Harbin Medical University, 150 Haping Rd, Harbin, Heilongjiang Province, People's Republic of China.

出版信息

Heliyon. 2024 Jul 4;10(13):e33902. doi: 10.1016/j.heliyon.2024.e33902. eCollection 2024 Jul 15.

Abstract

Photodynamic therapy (PDT) is attracting great attention for cancer treatments, while its therapeutic efficacy is limited by unsatisfactory photosensitizers and hypoxic tumor microenvironment (TME). To address these problems, we have developed catalase-loaded manganese-porphyrin frameworks (CAT@MnPFs) for catalytically-assisted PDT of cancer cells. CAT@MnPFs were constructed by the assembly of Mn ions and PpIX into MnPFs and the subsequent loading of catalase. Under 650 nm light irradiation, the porphyrin (Protoporphyrin IX) within the structure of CAT@MnPFs can convert oxygen (O) into singlet oxygen (O), showing the photodynamic effect. Importantly, the loaded catalase can decompose hydrogen peroxide (HO) into O with a huge elevation of O level (13.22 mg L) in 600 s, thus promoting O generation via PDT. As a result, CAT@MnPFs combined with 650 nm light can effectively ablate cancer cells due to the catalase-assisted oxygen-evolving PDT, showing a high therapeutic efficacy. Meanwhile, after the incubation with CAT@MnPFs, unobvious damage can be found in normal and red blood cells. Thus, the obtained CAT@MnPFs integrate the advantage of photosensitizers and catalase for oxygen-evolving PDT, which can provide some insight for treating hypoxic cells.

摘要

光动力疗法(PDT)在癌症治疗方面备受关注,但其治疗效果受到不理想的光敏剂和缺氧肿瘤微环境(TME)的限制。为了解决这些问题,我们开发了负载过氧化氢酶的锰卟啉框架(CAT@MnPFs)用于癌细胞的催化辅助光动力疗法。CAT@MnPFs通过将锰离子和原卟啉IX组装成MnPFs并随后负载过氧化氢酶构建而成。在650nm光照射下,CAT@MnPFs结构中的卟啉(原卟啉IX)可将氧气(O)转化为单线态氧(O),显示出光动力效应。重要的是,负载的过氧化氢酶可将过氧化氢(HO)分解为O,在600秒内使O水平大幅升高(13.22mg/L),从而通过光动力疗法促进O的产生。结果,由于过氧化氢酶辅助的析氧光动力疗法,CAT@MnPFs与650nm光结合可有效消融癌细胞,显示出高治疗效果。同时,与CAT@MnPFs孵育后,在正常细胞和红细胞中未发现明显损伤。因此,所获得的CAT@MnPFs整合了光敏剂和过氧化氢酶在析氧光动力疗法方面的优势,可为治疗缺氧细胞提供一些思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/765f/11282992/44ce88e1b094/sc1.jpg

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