Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, 15-222, Białystok, Poland.
Department of Microbiology and Immunology, The Faculty of Health Sciences of the Jan Kochanowski University in Kielce, 25-317, Kielce, Poland.
Sci Rep. 2017 Jul 4;7(1):4610. doi: 10.1038/s41598-017-04653-1.
Fungal infections caused by Candida spp. represent an emerging problem during treatment of immunocompromised patients and those hospitalized with serious principal diseases. The ever-growing number of fungal strains exhibiting drug resistance necessitates the development of novel antimicrobial therapies including those based on membrane-permeabilizing agents and nanomaterials as drug carriers. In this study, the fungicidal activities of LL-37 peptide, ceragenin CSA-13 and its magnetic derivatives (MNP@LL-37, MNP@CSA-13) against laboratory and clinical strains of C. albicans, C. glabrata and C. tropicalis were evaluated. These experiments confirm the high anti-fungal activity of these well-characterized agents mediated by their interaction with the fungal membrane and demonstrate elevated activity following immobilization of LL-37 and CSA-13 on the surface of magnetic nanoparticles (MNPs). Furthermore, MNP-based nanosystems are resistant to inhibitory factors present in body fluids and effectively inhibit formation of fungal biofilm. Simultaneously, synthesized nanostructures maintain immunomodulatory properties, described previously for free LL-37 peptide and CSA-13 substrate and they do not interfere with the proliferation and viability of osteoblasts, confirming their high biocompatibility.
白色念珠菌等真菌引起的感染是免疫功能低下患者和因严重基础疾病住院患者治疗过程中出现的一个新问题。具有抗药性的真菌菌株的数量不断增加,这就需要开发新的抗菌疗法,包括基于膜通透性剂和纳米材料的疗法,将其作为药物载体。在这项研究中,评估了 LL-37 肽、ceragenin CSA-13 及其磁性衍生物(MNP@LL-37、MNP@CSA-13)对实验室和临床分离的白色念珠菌、近平滑念珠菌和热带念珠菌的杀菌活性。这些实验证实了这些特征明确的试剂通过与真菌膜相互作用介导的高抗真菌活性,并证明了 LL-37 和 CSA-13 固定在磁性纳米颗粒(MNP)表面后活性提高。此外,基于 MNP 的纳米系统能够抵抗体液中存在的抑制因子,并能有效抑制真菌生物膜的形成。同时,合成的纳米结构保持了先前描述的游离 LL-37 肽和 CSA-13 基质的免疫调节特性,并且它们不干扰成骨细胞的增殖和活力,证实了它们的高生物相容性。