Department of Bioengineering, Northeastern University, Boston, MA 02115, USA; Nanomedicine Science and Technology Center, Northeastern University, Boston, MA 02115, USA.
Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA.
Biomaterials. 2017 Mar;119:78-85. doi: 10.1016/j.biomaterials.2016.12.011. Epub 2016 Dec 14.
The rising prevalence and severity of antibiotic-resistant biofilm infections poses an alarming threat to public health worldwide. Here, biocompatible multi-compartment nanocarriers were synthesized to contain both hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) and the hydrophilic antibiotic methicillin for the treatment of medical device-associated infections. SPION co-encapsulation was found to confer unique properties, enhancing both nanocarrier relaxivity and magneticity compared to individual SPIONs. These iron oxide-encapsulating polymersomes (IOPs) penetrated 20 μm thick Staphylococcus epidermidis biofilms with high efficiency following the application of an external magnetic field. Three-dimensional laser scanning confocal microscopy revealed differential bacteria death as a function of drug and SPION loading. Complete eradication of all bacteria throughout the biofilm thickness was achieved using an optimized IOP formulation containing 40 μg/mL SPION and 20 μg/mL of methicillin. Importantly, this formulation was selectively toxic towards methicillin-resistant biofilm cells but not towards mammalian cells. These novel iron oxide-encapsulating polymersomes demonstrate that it is possible to overcome antibiotic-resistant biofilms by controlling the positioning of nanocarriers containing two or more therapeutics.
抗生素耐药生物膜感染的发病率和严重程度不断上升，对全球公共健康构成了惊人的威胁。在这里，合成了生物相容性的多隔室纳米载体，以同时包含疏水性超顺磁性氧化铁纳米粒子（SPION）和亲水性抗生素甲氧西林，用于治疗与医疗器械相关的感染。发现 SPION 共包封赋予了独特的性质，与单独的 SPION 相比，提高了纳米载体的弛豫率和磁化率。在施加外部磁场后，这些氧化铁包封的聚合物囊泡（IOP）能够高效地穿透 20 μm 厚的表皮葡萄球菌生物膜。三维激光扫描共聚焦显微镜显示，药物和 SPION 负载的差异会导致细菌死亡。使用含有 40 μg/mL SPION 和 20 μg/mL 甲氧西林的优化 IOP 制剂可以实现整个生物膜厚度的所有细菌的完全消除。重要的是，这种制剂对甲氧西林耐药生物膜细胞具有选择性毒性，但对哺乳动物细胞没有毒性。这些新型氧化铁包封的聚合物囊泡表明，通过控制含有两种或更多治疗药物的纳米载体的定位，可以克服抗生素耐药生物膜。
