Enhanced Phototherapy by Nanoparticle-Enzyme via Generation and Photolysis of Hydrogen Peroxide

Enhanced Phototherapy by Nanoparticle-Enzyme via Generation and Photolysis of Hydrogen Peroxide
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纳米颗粒酶通过过氧化氢的产生和光解增强光疗

DOI:
10.1021/acs.nanolett.7b01382
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发表时间:
2017-07-01
期刊:
影响因子:
10.8
通讯作者:
Wu, Changfeng
Wu, Changfeng
中科院分区:
材料科学1区
文献类型:
--
作者:
Chang, Kaiwen;Liu, Zhihe;Wu, Changfeng

文献摘要

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光已广泛应用于癌症治疗,如光动力疗法(PDT)和光热疗法。本文介绍了一种称为酶增强光疗(EEPT)的策略。用于癌症治疗。我们通过葡萄糖氧化酶(GOx)与小聚合物点的共价偶联构建了一个纳米粒子平台,该平台可以持续固定在肿瘤中。而恶性肿瘤对葡萄糖的摄取较高,GOx能有效催化葡萄糖氧化,同时生成H2O2。在光照射下,原位生成的H2O2被光解生成羟基自由基,羟基自由基是活性最强的氧,杀死癌细胞。体外实验表明,纳米颗粒浓度为0.2 μ g/mL,光剂量约为120 J/cm(2),可以有效杀伤癌细胞,这表明在相同光剂量下,与典型的PDT相比,EEPT方法的效率显著提高,PDT需要10 μ g/mL的光敏剂才能有效杀伤细胞。此外,在携带异种移植物的小鼠中观察到显著的肿瘤生长抑制,表明EEPT方法用于癌症治疗的前景。
Light has been widely used for cancer therapeutics such as photodynamic therapy (PDT) and photothermal therapy. This paper describes a strategy called enzyme-enhanced phototherapy (EEPT). for cancer treatment. We constructed a nanoparticle platform by covalent conjugation of glucose oxidase (GOx) to small polymer dots, which could be persistently immobilized into a tumor. While the malignant tumors have high glucose uptake, the GOx efficiently catalyzes the glucose oxidation with simultaneous generation of H2O2. Under light irradiation, the in situ generated H2O2 was photolyzed to produce hydroxyl radical, the most reactive oxygen species, for killing cancer cells. In vitro assays indicated that the cancer cells were destroyed by using a nanoparticle concentration at 0.2 mu g/mL and a light dose of similar to 120 J/cm(2), indicating the significantly enhanced efficiency of the EEPT method when compared to typical PDT that requires a photosensitizer of >10 mu g/mL for effective cell killing under the same light dose. Furthermore, remarkable inhibition of tumor growth was observed in xenograft-bearing mice, indicating the promise of the EEPT approach for cancer therapeutics.