基于纳米颗粒的光动力抑制白色念珠菌生物膜并干扰群体感应,ACS Omega

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基于纳米颗粒的光动力抑制白色念珠菌生物膜并干扰群体感应
ACS Omega ( IF 3.7 ) Pub Date : 2023-01-17 , DOI: 10.1021/acsomega.2c07740
Na Tang ₁ , Shenghao Yuan ₂ , Yuxuan Luo ₂ , An-Jun Wang ₂ , Kang Sun ₁ , Ning-Ning Liu ₂ , Ke Tao ₁

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生物膜形成是白色念珠菌引起的真菌感染的发病机制和毒力的关键事件，导致抗真菌剂耐药性增加约 1000 倍。尽管光动力治疗 (PDT) 与细菌感染密切相关，但关于其通过清除真菌生物膜形成来对抗真菌感染的潜力的研究仍处于起步阶段。在这里，我们设计了具有不同尺寸、修饰和产生活性氧 (ROS) 能力的光动力纳米粒子，以检查它们对抑制生物膜形成和破坏白色念珠菌成熟生物膜的影响. 我们发现用寡聚壳聚糖修饰的纳米粒子对浮游细胞表现出更好的结合效率，从而导致更强的丝状化和早期生物膜形成抑制功效。然而，对于成熟的生物膜，最小尺寸（~15 nm）的纳米颗粒显示出最快的穿透速度和明显的破坏效果，尽管其产生 ROS 的能力最低。光动力纳米粒子的抑制作用取决于通过上调 ARO 8 和 DPP 3 表达介导的 QS 分子、法尼醇和酪醇对真菌群体感应 (QS) 的破坏。我们的研究结果提供了一种强大的纳米颗粒 PDT 策略，通过破坏 QS 抑制菌丝和生物膜形成来对抗真菌感染。

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Nanoparticle-Based Photodynamic Inhibition of Candida albicans Biofilms with Interfering Quorum Sensing

Biofilm formation is a critical event in the pathogenesis and virulence of fungal infections caused by Candida albicans, giving rise to about a 1000-fold increase in the resistance to antifungal agents. Although photodynamic treatment (PDT) has been excellently implicated in bacterial infections, studies on its potential against fungal infection through the clearance of fungal biofilm formation remain at its infancy stage. Here, we have designed photodynamic nanoparticles with different sizes, modifications, and the ability of generating reactive oxygen species (ROS) to examine their effects on inhibiting biofilm formation and destructing mature biofilms of C. albicans. We found that the nanoparticles modified with oligo-chitosan exhibited a better binding efficiency for planktonic cells, leading to stronger inhibitory efficacy of the filamentation and the early-stage biofilm formation. However, for mature biofilms, the nanoparticles with the smallest size (∼15 nm) showed the fastest penetration speed and a pronounced destructing effect albeit conferring the lowest ROS-producing capability. The inhibitory effect of photodynamic nanoparticles was dependent on the disruption of fungal quorum sensing (QS) by the upregulation of QS molecules, farnesol and tyrosol, mediated through the upregulation of ARO 8 and DPP 3 expression. Our findings provide a powerful strategy of nanoparticulate PDT to combat fungal infections through the inhibition of both hyphal and biofilm formation by disrupting QS.

更新日期：2023-01-17

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