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用于 HO 自供给化学动力学疗法治疗伤口感染的磁保持和葡萄糖供能羟基自由基纳米发电机。

Magnetically retained and glucose-fueled hydroxyl radical nanogenerators for HO-self-supplying chemodynamic therapy of wound infections.

机构信息

College of Life Science, State Key Laboratory of Developmental Biology of Freshwater Fish, Hunan Normal University, Changsha 410081, China.

Central Laboratory, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academic of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2021 Dec;131:112522. doi: 10.1016/j.msec.2021.112522. Epub 2021 Oct 26.

Abstract

Chemodynamic therapy (CDT) involving the highly toxic hydroxyl radical (OH) has exhibited tremendous potentiality in combating bacterial infection. However, its antibacterial efficacy is still unsatisfactory due to the insufficient HO levels and near neutral pH at infection site. Herein, a glucose-fueled and HO-self-supplying OH nanogenerator (pFeO@GOx) based on cascade catalytic reactions is developed by immobilizing glucose oxidase (GOx) on the surface of PAA-coated FeO (pFeO). Magnetic pFeO can act as a horseradish peroxidase-like nanozyme, catalyzing the decomposition of HO into OH under acidic conditions for CDT. The immobilized GOx can continuously convert non-toxic glucose into gluconic acid and HO, and the former improves the catalytic activity of pFeO nanozymes by decreasing pH value. The self-supplying HO molecules effectively enhance the OH generation, resulting in the high antibacterial efficacy. In vitro studies demonstrate that the pFeO@GOx conducts well in reducing pH value and improving HO level for self-enhanced CDT. Moreover, the cascade catalytic reaction of pFeO and GOx effectively avoids strong toxicity caused by directly adding high concentrations of HO for CDT. It is worth mentioning that the pFeO@GOx performs highly efficient in vivo CDT of bacteria-infected wound via the localized long-term magnetic retention at infection site and causes minimal toxicity to normal tissues at therapeutic doses. Therefore, the developed glucose-fueled OH nanogenerators are a potential nano-antibacterial agent for the treatment of wound infections.

摘要

化学动力学疗法(CDT)涉及到具有高毒性的羟基自由基(OH),在抗击细菌感染方面显示出巨大的潜力。然而,由于感染部位 HO 水平不足和接近中性 pH 值,其抗菌效果仍不理想。在此,通过将葡萄糖氧化酶(GOx)固定在聚(AA-共-马来酸)(PAA)包覆的 FeO(pFeO)表面上,开发了一种基于级联催化反应的葡萄糖驱动和 HO 自供应 OH 纳米发电机(pFeO@GOx)。磁性 pFeO 可以作为辣根过氧化物酶样纳米酶,在酸性条件下催化 HO 分解为 OH 用于 CDT。固定化的 GOx 可以将无毒的葡萄糖连续转化为葡萄糖酸和 HO,前者通过降低 pH 值来提高 pFeO 纳米酶的催化活性。自供应的 HO 分子有效地增强了 OH 的生成,从而提高了抗菌效果。体外研究表明,pFeO@GOx 能够很好地降低 pH 值并提高 HO 水平,从而实现自增强 CDT。此外,pFeO 和 GOx 的级联催化反应有效地避免了因直接添加高浓度 HO 而导致的强烈毒性。值得一提的是,pFeO@GOx 通过在感染部位的局部长期磁性保留,在体内对细菌感染伤口进行高效 CDT,并在治疗剂量下对正常组织的毒性最小。因此,开发的葡萄糖驱动的 OH 纳米发电机是治疗伤口感染的一种有潜力的纳米抗菌剂。

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