物理化学学报

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免刺激硒化钼量子点滴眼液杀菌抑炎协同干预真菌性角膜炎

耿熙炆1, 储丹丹1, 谷歆雨4, 张驰茵4, 潘湘蓉2, 苏雨蒙2, 栗占荣1, 周战2, 谭超良3, 李景果1,4   

  1. 1 河南省立眼科医院, 河南省人民医院, 郑州大学人民医院, 河南 郑州 450003;
    2 洛阳师范学院化学化工学院, 河南 洛阳 471934;
    3 香港城市大学电气工程系, 香港 999077;
    4 郑州大学材料科学与工程学院, 河南 郑州 450001
  • 收稿日期:2026-04-27 修回日期:2026-07-24 录用日期:2026-07-25
  • 通讯作者: 栗占荣, 周战, 谭超良, 李景果 E-mail:lizhanrong@zzu.edu.cn;zhouzhan@lynu.edu.cn;chaoltan@cityu.edu.hk;lijingguo@zzu.edu.cn
  • 基金资助:
    感谢河南省自然科学基金(242300421018、252300421044和252300421024)、国家自然科学基金(82371108和52173143)、河南省科技研发计划联合基金项目(242301420010)、河南省医学科技人才海外研修项目(HNMOT2024082)、河南省青年卫生健康科技创新人才培养项目(LJRC2024003)、河南省临床医学科学家培养计划(HNCMS202402)、香港城市大学启动基金(9610710)和国家贵金属材料工程技术研究中心香港分中心的资助。

Stimuli-free bifunctional MoSe2 quantum dots exert antifungal activity and mitigate inflammation for synergistic intervening fungal keratitis

Xiwen Geng1, Dandan Chu1, Xinyu Gu4, Chiyin Zhang4, Xiangrong Pan2, Yumeng Su2, Zhanrong Li1, Zhan Zhou2, Chaoliang Tan3, Jingguo Li1,4   

  1. 1 Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China;
    2 College of Chemistry and Chemical Engineering, Luoyang Normal University, Luoyang 471934, Henan Province, China;
    3 Department Electrical Engineering, Department Biomedical Engineering and Hong Kong Branch of National Precious Metals Material Engineering Research Center (NPMM), City University of Hong Kong, Hong Kong, China;
    4 School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, Henan Province, China
  • Received:2026-04-27 Revised:2026-07-24 Accepted:2026-07-25
  • Contact: Zhanrong Li, Zhan Zhou, Chaoliang Tan, Jingguo Li E-mail:lizhanrong@zzu.edu.cn;zhouzhan@lynu.edu.cn;chaoltan@cityu.edu.hk;lijingguo@zzu.edu.cn

摘要: 真菌性角膜炎(FK)的有效治疗迫切需要创新策略,将强效抗真菌活性与显著的抗炎作用相结合,以克服日益严重的真菌耐药性和角膜穿透障碍,从而预防角膜纤维化和视力丧失。在此,我们开发了一种超小尺寸的二硒化钼(MoSe2)量子点滴眼液(MSQD),作为一种无刺激的双功能平台。MSQD对腐皮镰刀菌的最低抑菌浓度(MIC)低至0.05 μg mL-1,比传统一线药物伏立康唑(Vor,MIC 11.76 μg mL-1)低235倍。MSQD表现出快速且完全的杀菌活性,可以通过诱导细胞内氧化还原崩溃和不可逆的膜损伤,在1 h内实现100%的病原菌清除。此外,MSQD自身具有类过氧化氢酶(CAT)催化活性,能有效清除细胞内活性氧,减轻炎症,并形成促进愈合的角膜微环境。同时,MSQD的量子尺寸可以通过短暂性地调节细胞连接促进深层角膜穿透,从而确保其被高效递送至感染部位。在小鼠FK模型中,经MSQD治疗的眼睛实现了病原体的完全清除,并恢复了与健康组织无异的角膜透明度,与Vor相比表现出更高的生物利用度和优越的治疗效果。总之,这些多方面的特性使无刺激的MSQD成为一种新型、高效且安全的抗菌抗炎双功能纳米平台,兼具卓越的效力和优异的生物相容性,为真菌感染的综合治疗带来了巨大前景。

关键词: MoSe2量子点, 滴眼液, 真菌性角膜炎, 缓解炎症, 量子限制效应

Abstract: Effective management of fungal keratitis (FK) urgently demands innovative strategies integrating potent antifungal activity with robust anti-inflammatory effects to overcome rising antifungal resistance and corneal penetration barriers, preventing corneal fibrosis and vision loss. Herein, we develop an ultrasmall molybdenum diselenide (MoSe2) quantum dot eye drop (MSQD) as a stimuli-free bifunctional platform. The MSQD exhibits an ultra-low minimum inhibitory concentration (MIC) of 0.05 μg mL-1 against Fusarium solani, approximately 235-fold lower than the conventional first-line agent voriconazole (Vor, MIC 11.76 μg mL-1). The MSQD demonstrates rapid and complete fungicidal activity, achieving 100% cell elimination within 1 h by inducing intracellular redox collapse and irreversible membrane damage. Furthermore, the MSQD possesses intrinsic catalase (CAT)-mimetic activities, efficiently scavenging intracellular reactive oxygen species, alleviating inflammation, and promoting a pro-healing corneal microenvironment. In addition, the quantum dimensions of MSQD facilitate deep corneal penetration through transient cell junction modulation, thus ensuring efficient delivery to the infection sites. In a mouse FK model, MSQD-treated eyes achieve complete pathogen eradication and restore corneal clarity indistinguishable from healthy tissue, exhibiting great bioavailability and a superior therapeutic effect compared to Vor. Collectively, these multifaceted attributes establish stimuli-free MSQD as a novel, highly efficient and safe bifunctional nanoplatform with superior potency and excellent biocompatibility, holding great promise for comprehensive management of fungal infections.

Key words: MoSe2 quantum dots, Eye drops, Fungal keratitis, Inflammation eliminating, Quantum confinement