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在治疗感染性角膜炎时,采用无抗生素的眼部消毒来抑制免疫反应,以保护角膜透明。

Antibiotic-free ocular sterilization while suppressing immune response to protect corneal transparency in infectious keratitis treatment.

机构信息

National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325000, China.

First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

出版信息

J Control Release. 2024 Oct;374:563-576. doi: 10.1016/j.jconrel.2024.08.038. Epub 2024 Aug 30.

Abstract

Clinical guidelines for infectious keratitis treatment require that anti-inflammatory drugs can only be used after infection elimination, which causes irreversible inflammatory damage to the cornea. In this work, photodynamic metal organic frameworks (PCN-224) were used as drug carrier to load Pt NPs with catalase-like activity and anti-inflammatory drug (Dexamethasone, DXMS) for endogenous oxygen generation and reduced corneal damage, respectively. The photodynamic therapy (PDT) effect was greatly enhanced in bacteria elimination and bacterial biofilms removal through catalysis of overexpressed hydrogen peroxide (HO, ∼8.0 and 31.0 μM in bacterial solution and biofilms, respectively) into oxygen by Pt NPs. More importantly, the cationic liposome modified PCN-224@Pt@DXMS@Liposomes (PPDL NPs) greatly enhanced the adhesion to negatively charged ocular surface and penetration into corneal barrier and bacterial biofilms. Both in vitro cell viability test and in vivo eye irritation tests proved good biocompatibility of PPDL NPs under 660 nm laser irradiation. Furthermore, PDT of PPDL NPs in rapid bacteria killing was verified through infectious keratitis animal model. The superior bactericidal effect of antibacterial materials could largely replace the bactericidal effect of the immune system. It is worth mentioning that this simultaneous sterilization and anti-inflammation treatment mode is a new exploration against the clinical treatment guidelines.

摘要

临床传染性角膜炎治疗指南要求在消除感染后才能使用抗炎药物,这会导致角膜不可逆的炎症损伤。在这项工作中,光动力金属有机骨架(PCN-224)被用作药物载体,分别负载具有过氧化氢酶样活性的 Pt NPs 和抗炎药物(地塞米松,DXMS),以实现内源性氧气生成和减轻角膜损伤。Pt NPs 将过量表达的过氧化氢(HO,在细菌溶液和生物膜中分别约为 8.0 和 31.0 μM)催化转化为氧气,大大增强了细菌消除和细菌生物膜去除的光动力疗法(PDT)效果。更重要的是,阳离子脂质体修饰的 PCN-224@Pt@DXMS@Liposomes(PPDL NPs)大大增强了对带负电荷的眼表的黏附性和对角膜屏障和细菌生物膜的穿透性。在 660nm 激光照射下,体外细胞活力测试和体内眼刺激性测试均证明了 PPDL NPs 的良好生物相容性。此外,通过感染性角膜炎动物模型验证了 PPDL NPs 的快速杀菌 PDT。抗菌材料的优越杀菌效果可以在很大程度上替代免疫系统的杀菌效果。值得一提的是,这种同时杀菌和抗炎的治疗模式是对临床治疗指南的新探索。

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