Centre of Biological Engineering, University of Minho (CEB), Campus de Gualtar, 4710-057 Braga, Portugal.
LABBELS - Associate Laboratory, Braga, Guimarães, Portugal.
J Mater Chem B. 2024 Nov 13;12(44):11464-11476. doi: 10.1039/d4tb00903g.
In this work, an expedite synthesis was developed for a self-assembled micelle carrier for the antimicrobial peptide LL18. Covalent one-pot functionalization of dextrin with succinylated vitamin D3 and succinic anhydride produced an amphiphilic material that undergoes self-assembly into micelles in aqueous medium. Succinylated dextrin-vitamin D3 micelles were efficiently loaded with LL18 by electrostatic and hydrophobic interactions. Remarkably, the LL18-loaded micelle formulation dramatically improves the antibacterial activity of free LL18 against , completely abrogates its severe hemolytic activity, redirects the internalization of LL18 from the perinuclear region of osteoblasts to the lysosomes and reduces cellular toxicity towards osteoblasts and macrophages. Overall, this work demonstrates that self-assembled micelle formulations based on dextrin, vitamin D3 and antimicrobial peptides, are promising platforms to develop multifunctional antibiotic-independent antimicrobial agents, not prone to the development of bacterial resistance, to treat bone infections.
在这项工作中，开发了一种用于抗菌肽 LL18 的自组装胶束载体的快速合成方法。通过与琥珀酰化维生素 D3 和琥珀酸酐的共价一锅法功能化，得到了一种两亲性材料，该材料在水介质中自组装成胶束。通过静电和疏水相互作用，琥珀酰化葡聚糖-维生素 D3 胶束能够有效地将 LL18 加载进去。值得注意的是，负载 LL18 的胶束制剂显著提高了游离 LL18 对 的抗菌活性，完全消除了其严重的溶血活性，将 LL18 的内化从成骨细胞的核周区域重定向到溶酶体，并降低了其对成骨细胞和巨噬细胞的细胞毒性。总的来说，这项工作表明，基于葡聚糖、维生素 D3 和抗菌肽的自组装胶束制剂是开发多功能、不依赖抗生素的抗菌剂的有前途的平台，不易产生细菌耐药性，可用于治疗骨感染。
