Valentin Jules D P, Kadakia Parth, Varidel Lucie J, Stuart Marc C A, Salentinig Stefan
Department of Chemistry and National Center of Competence in Research Bio-inspired Materials, University of Fribourg, Chemin du Musée 9, Fribourg, 1700, Switzerland.
Centre for System Chemistry, Stratingh Institute for Chemistry and Groningen Biomolecular Science and Biotechnology Institute, University of Groningen, Nijenborgh 7, Groningen, 9747AG, The Netherlands.
Small. 2024 Dec;20(51):e2405131. doi: 10.1002/smll.202405131. Epub 2024 Oct 15.
The antimicrobial peptide LL-37 is a promising alternative to conventional antibiotics to combat bacteria in suspension and biofilms. Its self-assembly with polar lipids is suggested to improve its potential for therapeutic applications with higher stability against degradation and bioavailability. This study investigates the self-assembly of LL-37 with glyceryl monooleate (GMO), establishing the link between colloidal structure and antimicrobial activity. Small-angle X-ray scattering, dynamic light scattering and cryogenic transmission electron microscopy show structural transformation from dispersions of inverse bicontinuous structure (cubosomes) to multilamellar vesicles and direct rod-like mixed-micelles upon increasing the content of LL-37 in GMO. In vitro assays against planktonic and biofilm cells demonstrate that 128 µg mL of GMO cubosomes have no impact on Pseudomonas aeruginosa. Still, the cubosomes reduce the Staphylococcus aureus planktonic population by ≈ 1-log after 24 h. Cylindrical micelles formed at LL-37/GMO 9/1 and 8/2 with 128 µg mL LL-37 decrease the Pseudomonas aeruginosa population by 6-log. This activity is gradually abolished when LL-37 is encapsulated in vesicles or cubosomes. They also demonstrate low antibiofilm efficacy and promote the biomass of Staphylococcus aureus biofilms. These results highlight the importance of colloidal structure for therapeutic outcomes, providing insights for advanced lipid nanocarrier designs.
抗菌肽LL-37是对抗悬浮细菌和生物膜的传统抗生素的一种有前景的替代品。它与极性脂质的自组装被认为可以提高其治疗应用潜力，具有更高的抗降解稳定性和生物利用度。本研究调查了LL-37与单油酸甘油酯（GMO）的自组装，建立了胶体结构与抗菌活性之间的联系。小角X射线散射、动态光散射和低温透射电子显微镜显示，随着LL-37在GMO中含量的增加，结构从反相双连续结构（立方相）分散体转变为多层囊泡和直接的棒状混合胶束。针对浮游细胞和生物膜细胞的体外试验表明，128 µg/mL的GMO立方相脂质体对铜绿假单胞菌没有影响。不过，立方相脂质体在24小时后可使金黄色葡萄球菌浮游菌数量减少约1个对数级。在LL-37/GMO为9/1和8/2且LL-37浓度为128 µg/mL时形成的圆柱形胶束可使铜绿假单胞菌数量减少6个对数级。当LL-37被包裹在囊泡或立方相脂质体中时，这种活性会逐渐消失。它们还显示出低抗生物膜功效，并促进金黄色葡萄球菌生物膜的生物量。这些结果突出了胶体结构对治疗效果的重要性，为先进的脂质纳米载体设计提供了见解。
