Background: The constant rise of microbial biofilm formation and drug resistance to existing antimicrobial drugs poses a significant threat to community health around the world because it reduces the efficacy and efficiency of treatments, increasing morbidity, mortality, and health-care expenditures. As a result, there is an urgent need to develop novel antimicrobial agents that inhibit microbial biofilm formation.
Methods: The [Ni_0.4Cu_0.2Zn_0.4](Fe_2-xDy_x)O₄(x≤ 0.04) (Ni-Cu-Zn) nano spinel ferrites (NSFs) have been synthesized by the sol–gel auto-combustion process and were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive x-ray (EDX) and transmission electron microscopy (TEM). The antimicrobial, antibiofilm and antiproliferative activities of Ni-Cu-Zn NSFs were also examined.
Results: The XRD pattern confirms the secondary phase DyFeO₃ and Fe₂O₃ for substituted Dy³⁺ samples, and the crystallite size ranged from 10 to 19 nm. TEM analysis of NSFs revealed that the particles were cube-shaped and 15nm in size. NSFs exhibited significant antimicrobial, antibiofilm and antiproliferative activity. At concentration of 1 mg/mL, it was found that the NSFs (ie, x=0.0, x=0.01, x=0.02, x=0.03 and x=0.04) inhibit biofilm formation by 27.6, 26.2, 58.5, 33.3 and 25% for methicillin-resistant Staphylococcus aureus (MRSA) and 47.5, 43.5, 48.6, 58.3 and 26.6% for Candida albicans, respectively. SEM images demonstrate that treating MRSA and C. albicans biofilms with NSFs significantly reduces cell adhesion, colonization and destruction of biofilm architecture and extracellular polymeric substances matrices. Additionally, SEM and TEM examination revealed that NSFs extensively damaged the cell walls and membranes of MRSA and C. albicans. Huge ultrastructural alteration such as deformation, disintegration and separation of cell wall and membrane from the cells was observed, indicating significant loss of membrane integrity, which eventually led to cell death. Furthermore, it was observed that NSF inhibited the cancer cell growth and proliferation of HCT-116 in a dose-dependent manner.
Conclusion: The current study demonstrated that the synthesized Ni-Cu-Zn NSFs could be used to develop potential antimicrobial surface coatings agents for a varieties of biomedical-related materials and devices in order to prevent the biofilms formation and their colonization. Furthermore, the enhanced antiproliferative properties of manufactured SNFs suggest a wide range of biomedical applications.



中文翻译：

---

Dy取代Ni0.4Cu0.2Zn0.4(Fe2-xDyx)O4纳米尖晶石铁氧体的溶胶-凝胶合成及其抗菌、抗真菌、抗生物膜和抗癌潜力的生物医学应用评价

背景：微生物生物膜形成和对现有抗菌药物耐药性的不断增加对世界各地的社区健康构成了重大威胁，因为它降低了治疗的功效和效率，增加了发病率、死亡率和医疗保健支出。因此，迫切需要开发抑制微生物生物膜形成的新型抗菌剂。
方法： [Ni _0.4 Cu _0.2 Zn _0.4 ](Fe _2-x Dy _x )O ₄(x≤0.04) (Ni-Cu-Zn) 纳米尖晶石铁氧体 (NSFs) 采用溶胶-凝胶自燃工艺合成，并通过 X 射线衍射 (XRD)、扫描电子显微镜 (SEM)、能量色散 X 射线 (EDX) 和透射电子显微镜 (TEM)。还检查了 Ni-Cu-Zn NSFs 的抗菌、抗生物膜和抗增殖活性。
结果： XRD图证实了取代的Dy ^{3 +的第二相DyFeO} ₃和Fe ₂ O ₃样品，微晶尺寸范围为 10 至 19 nm。NSF 的 TEM 分析显示，这些颗粒呈立方体形状，尺寸为 15nm。NSFs 表现出显着的抗菌、抗生物膜和抗增殖活性。在 1 mg/mL 的浓度下，发现 NSF（即 x=0.0、x=0.01、x=0.02、x=0.03 和 x=0.04）抑制生物膜形成 27.6、26.2、58.5、33.3 和 25耐甲氧西林金黄色葡萄球菌(MRSA) 和白色念珠菌分别为 47.5、43.5、48.6、58.3 和 26.6% 。SEM 图像表明，治疗 MRSA 和白色念珠菌具有 NSF 的生物膜显着降低了生物膜结构和细胞外聚合物基质的细胞粘附、定植和破坏。此外，SEM 和 TEM 检查显示 NSF 广泛破坏了 MRSA 和白色念珠菌的细胞壁和细胞膜。观察到巨大的超微结构改变，例如细胞壁和细胞膜的变形、解体和分离，表明细胞膜完整性显着丧失，最终导致细胞死亡。此外，观察到 NSF 以剂量依赖性方式抑制 HCT-116 的癌细胞生长和增殖。
结论：目前的研究表明，合成的 Ni-Cu-Zn NSFs 可用于开发用于各种生物医学相关材料和装置的潜在抗菌表面涂层剂，以防止生物膜的形成及其定植。此外，人造 SNF 增强的抗增殖特性表明其具有广泛的生物医学应用。