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用于精准真菌治疗学的仿生多功能纳米复合材料。

Biomimetic and multifunctional nanocomposites for precision fungi theranostics.

机构信息

School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, PR China.

Department of Obstetrics and Gynecology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, PR China.

出版信息

Biomaterials. 2024 Jul;308:122561. doi: 10.1016/j.biomaterials.2024.122561. Epub 2024 Apr 4.

DOI:10.1016/j.biomaterials.2024.122561
PMID:38603827
Abstract

Fungi infection is a serious threat to public health, but an effective antifungal strategy remains a challenge. Herein, a biomimetic nanocomposite with multifunctionalities, including fungi diagnosis, antifungal adhesion, precise fungi elimination, and cytokine sequestration, is constructed for battling Candida albicans (C. albicans) infection. By screening a range of cells, we find that the polarized macrophage cells have the strongest binding tendency toward C. albicans. Thus, their membranes were exfoliated to camouflage UCNPs and then decorated with photosensitizers (methylene blue, MB) and DNA sensing elements. The resulting nanocomposite can tightly bind to fungal surfaces, promote DNA recognition, and squeeze pro-inflammatory cytokines to relieve inflammation. Consequently, this nanocomposite can detect C. albicans with enhanced sensitivity and precisely eliminate fungal cells through photodynamic therapy with minimal phototoxicity because of its switchable fluorescence behavior. The developed nanocomposite with good biocompatibility achieves a satisfactory diagnostic and therapeutic effect in a C. albicans-infected mouse model, which offers a unique approach to fight fungi infection.

摘要

真菌感染是严重威胁公众健康的问题,但目前仍缺乏有效的抗真菌策略。本研究构建了一种具有诊断真菌、抗真菌黏附、精准消除真菌和细胞因子隔离等多功能的仿生性纳米复合材料,用于治疗白色念珠菌(Candida albicans,C. albicans)感染。通过筛选一系列细胞,我们发现极化的巨噬细胞对 C. albicans 具有最强的结合倾向。因此,我们将其细胞膜剥离以伪装上上近红外上转换纳米颗粒(upconversion nanoparticles,UCNPs),然后用光敏剂(亚甲蓝,MB)和 DNA 传感元件进行修饰。所得的纳米复合材料可以紧密结合真菌表面,促进 DNA 识别,并挤出促炎细胞因子以减轻炎症。因此,由于其可切换的荧光行为,这种纳米复合材料具有增强的灵敏度,可以通过光动力疗法以最小的光毒性精确消除真菌细胞。该具有良好生物相容性的纳米复合材料在白色念珠菌感染的小鼠模型中实现了令人满意的诊断和治疗效果,为抗真菌感染提供了一种独特的方法。

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