聚合物纳米颗粒(NP)作为靶向药物递送的生物医学纳米载体呈现一些理想的性质,例如通过身体屏障的增强易位。生物聚合物,如聚羟基链烷酸酯(PHA)作为纳米载体生物材料,由于其固有的生物相容性而受到关注,生物降解性,以及通过疏水介质被车辆化的能力,例如肺表面活性剂(LS)。在肺泡定植后,在LS层下面,肺炎链球菌,导致社区获得性肺炎,严重的呼吸道疾病.在这项工作中,我们通过固定化酶将PHANPs转化为抗菌物质,一种抗菌酶,通过最小的PHA亲和标签。我们首先产生融合蛋白M711,包含最小化的PHA亲和标签,MinP,和特异性靶向肺炎链球菌的酶菌Cpl-711。然后,配制了具有足够物理化学性质的用于肺部递送的PHA纳米颗粒悬浮液,NPs用M711装饰。最后,我们评估了纳米系统对浮游和生物膜形式的肺炎链球菌的抗肺炎球菌活性.所得到的系统显示出持续的抗微生物活性,自由和无柄细胞,证实标签介导的酶在PHAs上的固定是生物活性抗菌功能的有前途的平台。
Polymeric nanoparticles (NPs) present some ideal properties as biomedical nanocarriers for targeted drug delivery such as enhanced translocation through body barriers. Biopolymers, such as polyhydroxyalkanoates (PHAs) are gaining attention as nanocarrier biomaterials due to their inherent biocompatibility, biodegradability, and ability to be vehiculized through hydrophobic media, such as the lung surfactant (LS). Upon colonization of the lung alveoli, below the LS layer, Streptococcus pneumoniae, causes community-acquired pneumonia, a severe respiratory condition. In this work, we convert PHA NPs into an antimicrobial material by the immobilization of an enzybiotic, an antimicrobial enzyme, via a minimal PHA affinity tag. We first produced the fusion protein M711, comprising the minimized PHA affinity tag, MinP, and the enzybiotic Cpl-711, which specifically targets S. pneumoniae. Then, a PHA nanoparticulate suspension with adequate physicochemical properties for pulmonary delivery was formulated, and NPs were decorated with M711. Finally, we assessed the antipneumococcal activity of the nanosystem against planktonic and biofilm forms of S. pneumoniae. The resulting system displayed sustained antimicrobial activity against both, free and sessile cells, confirming that tag-mediated immobilization of enzybiotics on PHAs is a promising platform for bioactive antimicrobial functionalization.