Abstract The prevalence and fatality rates with fungal biofilm-associated infections urgently need to develop targeted therapeutic approaches to augment the action of antifungal drugs. This study developed amphotericin B-loaded PLGA-PEG nanoparticles (AmB-NPs) with AD1 aptamer conjugation on its surface via an EDC/NHS technique. Their high nuclease resistance of the conjugation was confirmed by PAGE gel electrophoresis. The targeting and toxicity of AD1-AmB-NPs in the subcutaneous C. albicans infection model were evaluated. AD1-AmB-NPs can bind to different morphological forms(including yeast cells, germ tubes, hyphae) of C. albicans biofilms and extracellular matrix material. Low-frequency and low-intensity ultrasound (LFU, with a fixed frequency of 42 kHz, at the intensity of 0.30 W/cm2 for 15 min) significantly promoted permeability of the biofilm and allowed AD1-AmB-NPs into the deepest layers of the biofilm. After 7 days of treatment, the combination treatment of AD1-AmB-NPs and LFU, kills at least 99% of the biofilm fungal population in vivo comparison with ultrasound alone or AD1-AmB-NPs alone, and returned to normal subcutaneously. Our data suggest that the combined strategy of AD1-AmB-NPs and ultrasound treatment selective delivered of therapeutic drugs to the infection site and exhibited significant synergistic antifungal effects.

中文翻译：

---

AD1适体功能化两性霉素B负载PLGA-PEG纳米粒通过靶向作用增强低频和低强度超声暴露对白色念珠菌生物膜的抗真菌作用

摘要 真菌生物膜相关感染的患病率和死亡率迫切需要开发有针对性的治疗方法来增强抗真菌药物的作用。本研究通过 EDC/NHS 技术开发了负载两性霉素 B 的 PLGA-PEG 纳米颗粒 (AmB-NPs)，其表面具有 AD1 适体缀合。PAGE凝胶电泳证实了它们对缀合的高核酸酶抗性。评估了 AD1-AmB-NPs 在皮下白色念珠菌感染模型中的靶向性和毒性。AD1-AmB-NPs可以与白色念珠菌生物膜和细胞外基质材料的不同形态（包括酵母细胞、胚管、菌丝）结合。低频低强度超声（LFU，固定频率为 42 kHz，强度为 0. 30 W/cm2 持续 15 分钟）显着促进了生物膜的渗透性，并允许 AD1-AmB-NPs 进入生物膜的最深层。治疗 7 天后，AD1-AmB-NPs 和 LFU 的联合治疗与单独使用超声或单独使用 AD1-AmB-NPs 相比，在体内杀死至少 99% 的生物膜真菌群，并在皮下恢复正常。我们的数据表明，AD1-AmB-NPs 和超声治疗的联合策略选择性地将治疗药物输送到感染部位，并表现出显着的协同抗真菌作用。并在皮下恢复正常。我们的数据表明，AD1-AmB-NPs 和超声治疗的联合策略选择性地将治疗药物输送到感染部位，并表现出显着的协同抗真菌作用。并在皮下恢复正常。我们的数据表明，AD1-AmB-NPs 和超声治疗的联合策略选择性地将治疗药物输送到感染部位，并表现出显着的协同抗真菌作用。