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Highly Effective Antibacterial Vesicles Based on Peptide-Mimetic Alternating Copolymers for Bone Repair
Biomacromolecules ( IF 6.2 ) Pub Date : 2017-10-23 00:00:00 , DOI: 10.1021/acs.biomac.7b01209
Chuncai Zhou 1, 2 , Yue Yuan 2 , Panyu Zhou 3 , Fangyingkai Wang 2 , Yuanxiu Hong 2 , Nuosha Wang 2 , Shuogui Xu 3 , Jianzhong Du 1, 2
Affiliation  

It is an important challenge for bone repair to effectively deliver growth factors and at the same time to prevent and cure inflammation without obvious pathogen resistance. We designed a kind of antibacterial peptide-mimetic alternating copolymers (PMACs) to effectively inhibit and kill both Gram-positive and Gram-negative bacteria. The minimum inhibition concentrations (MICs) of the PMACs against E. coli and S. aureus are 8.0 μg/mL, which are much lower than that of antibacterial peptides synthesized by other methods such as widely used ring-opening polymerization of N-carboxyanhydride. Furthermore, the PMACs can self-assemble into polymer vesicles (polymersomes) in pure water with low cytotoxicity (IC50 > 1000 μg/mL), which can encapsulate growth factors in aqueous solution and release them during long-term antibacterial process for facilitating bone repair. We also find that the alternating structure is essential for the excellent antibacterial activity. The in vivo tests in rabbits confirmed that the growth-factor-encapsulated antibacterial vesicles have better bone repair ability compared with control groups without antibacterial vesicles. Overall, we have provided a novel method for designing PMAC-based highly effective intrinsically antibacterial vesicles that may have promising biomedical applications in the future.

中文翻译:

基于肽模拟交替共聚物的高效抗菌小泡,可修复骨。

在没有明显的病原体抵抗力的情况下,有效地传递生长因子并同时预防和治疗炎症是骨修复的一项重要挑战。我们设计了一种抗菌肽模拟交替共聚物(PMAC),以有效抑制和杀死革兰氏阳性和革兰氏阴性细菌。PMAC对大肠杆菌金黄色葡萄球菌的最小抑制浓度(MIC)为8.0μg / mL,远低于通过其他方法(如广泛使用的N-羧基酐的开环聚合反应)合成的抗菌肽的抑制浓度。此外,PMAC可以在纯水中自组装成具有低细胞毒性的聚合物囊泡(聚合物囊泡)(IC 50> 1000μg/ mL),可以将生长因子包裹在水溶液中,并在长期抗菌过程中释放出来,以促进骨骼修复。我们还发现,交替的结构对于出色的抗菌活性至关重要。兔体内试验证实,与不含抗菌小泡的对照组相比,生长因子包埋的抗菌小泡具有更好的骨修复能力。总体而言,我们提供了一种新颖的方法来设计基于PMAC的高效内在抗菌小泡,这些小泡在未来可能具有广阔的生物医学应用前景。
更新日期:2017-10-24
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