Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, Ghent, Belgium; LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, Porto, Portugal; i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, Ghent, Belgium.
Biomaterials. 2017 Sep;138:1-12. doi: 10.1016/j.biomaterials.2017.05.029. Epub 2017 May 20.
The rising antimicrobial resistance contributes to 25000 annual deaths in Europe. This threat to the public health can only be tackled if novel antimicrobials are developed, combined with a more precise use of the currently available antibiotics through the implementation of fast, specific, diagnostic methods. Nucleic acid mimics (NAMs) that are able to hybridize intracellular bacterial RNA have the potential to become such a new class of antimicrobials and additionally could serve as specific detection probes. However, an essential requirement is that these NAMs should be delivered into the bacterial cytoplasm, which is a particular challenge given the fact that they are charged macromolecules. We consider these delivery challenges in relation to the gastric pathogen Helicobacter pylori, the most frequent chronic infection worldwide. In particular, we evaluate if cationic fusogenic liposomes are suitable carriers to deliver NAMs across the gastric mucus barrier and the bacterial envelope. Our study shows that DOTAP-DOPE liposomes post-PEGylated with DSPE-PEG (DSPE Lpx) can indeed successfully deliver NAMs into Helicobacter pylori, while offering protection to the NAMs from binding and inactivation in gastric mucus isolated from pigs. DSPE Lpx thus offer exciting new possibilities for in vivo diagnosis and treatment of Helicobacter pylori infections.
抗菌药物耐药性的不断上升导致欧洲每年有 25000 人死亡。如果要解决这一对公众健康的威胁，就必须开发新型抗菌药物，并通过实施快速、特异的诊断方法，更精确地使用现有的抗生素。能够与细菌内源性 RNA 杂交的核酸类似物（NAMs）有潜力成为新一类的抗菌药物，并且还可以作为特异的检测探针。然而，一个必要的要求是这些 NAMs 应该被递送到细菌细胞质中，鉴于它们是带电荷的大分子，这是一个特殊的挑战。我们考虑了与胃病原体幽门螺杆菌相关的这些递药挑战，这是全世界最常见的慢性感染。特别地，我们评估了阳离子融合脂质体是否适合作为载体，将 NAMs 递送到胃粘液屏障和细菌包膜中。我们的研究表明，经过聚乙二醇化的 DOTAP-DOPE 脂质体（DSPE Lpx）确实可以成功地将 NAMs 递送到幽门螺杆菌中，同时还可以保护 NAMs 免受结合和失活，这些 NAMs 是在从猪中分离的胃粘液中。因此，DSPE Lpx 为幽门螺杆菌感染的体内诊断和治疗提供了令人兴奋的新可能性。
