School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510000, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China.
Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan 030001, China.
J Control Release. 2024 Nov;375:627-642. doi: 10.1016/j.jconrel.2024.09.022. Epub 2024 Sep 23.
Methicillin-Resistant Staphylococcus aureus forming into biofilms can trigger chronic inflammation and disrupt skin wound healing processes. Prolonged and excessive use of antibiotics can expedite the development of resistance, primarily because of their limited ability to penetrate microbial membranes and biofilms, especially antibiotics with intracellular drug targets. Herein, we devise a strategy in which virus-inspired nanoparticles control the release of antibiotics through rapid penetration into both bacterial cells and biofilms, thereby combating antimicrobial-resistant infections and promoting skin wound healing. Lipid-based nanoparticles based on stearamine and cholesterol were designed to mimic viral highly ordered nanostructures. To mimic the arginine-rich fragments in viral protein transduction domains, the primary amines on the surface of the lipid-based nanoparticles were exchanged by guanidine segments. Levofloxacin, an antibiotic that inhibits DNA replication, was chosen as the model drug to be incorporated into nanoparticles. Hyaluronic acid was coated on the surface of nanoparticles acting as a capping agent to achieve bacterial-specific degradation and guanidine explosion in the bacterial microenvironment. Our virus-inspired nanoparticles displayed long-acting antibacterial effects and powerful biofilm elimination to overcome antimicrobial-resistant infections and promote skin wound healing. This work demonstrates the ability of virus-inspired nanoparticles to achieve a dual penetration of microbial cell membranes and biofilm structures to address antimicrobial-resistant infections and trigger skin wound healing.
耐甲氧西林金黄色葡萄球菌形成生物膜会引发慢性炎症，并破坏皮肤伤口愈合过程。抗生素的长期、过度使用会加速耐药性的发展，这主要是因为抗生素穿透微生物膜和生物膜的能力有限，尤其是针对具有细胞内药物靶点的抗生素。在本研究中，我们设计了一种策略，即通过快速穿透细菌细胞和生物膜，利用病毒启发的纳米颗粒来控制抗生素的释放，从而对抗抗微生物感染并促进皮肤伤口愈合。基于硬脂胺和胆固醇的脂质纳米颗粒被设计用来模拟病毒的高度有序纳米结构。为了模拟病毒蛋白转导结构域中富含精氨酸的片段，脂质纳米颗粒表面的伯胺被胍基片段取代。左氧氟沙星是一种抑制 DNA 复制的抗生素，被选择作为模型药物被包载于纳米颗粒中。透明质酸被涂覆在纳米颗粒表面，作为一种封闭剂，以实现在细菌微环境中实现细菌特异性降解和胍基爆炸。我们设计的病毒启发纳米颗粒具有长效的抗菌作用和强大的生物膜消除作用，能够克服抗微生物感染并促进皮肤伤口愈合。本工作展示了病毒启发纳米颗粒穿透微生物细胞膜和生物膜结构的双重能力，以解决抗微生物感染和触发皮肤伤口愈合的问题。
