Duong Hien T T, Jung Kenward, Kutty Samuel K, Agustina Sri, Adnan Nik Nik M, Basuki Johan S, Kumar Naresh, Davis Thomas P, Barraud Nicolas, Boyer Cyrille
Australian Centre for Nanomedicine and ‡Centre for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, §School of Chemistry, and ∥Centre for Marine Bio-Innovation, School of Biotechnology and Biomolecular Sciences, University of New South Wales , Sydney, New South Wales, Australia 2052.
Biomacromolecules. 2014 Jul 14;15(7):2583-9. doi: 10.1021/bm500422v. Epub 2014 Jun 10.
Biofilms are increasingly recognized as playing a major role in human infectious diseases, as they can form on both living tissues and abiotic surfaces, with serious implications for applications that rely on prolonged exposure to the body such as implantable biomedical devices or catheters. Therefore, there is an urgent need to develop improved therapeutics to effectively eradicate unwanted biofilms. Recently, the biological signaling molecule nitric oxide (NO) was identified as a key regulator of dispersal events in biofilms. In this paper, we report a new class of core cross-linked star polymers designed to store and release nitric oxide, in a controlled way, for the dispersion of biofilms. First, core cross-linked star polymers were prepared by reversible addition-fragmentation chain transfer polymerization (RAFT) via an arm first approach. Poly(oligoethylene methoxy acrylate) chains were synthesized by RAFT polymerization, and then chain extended in the presence of 2-vinyl-4,4-dimethyl-5-oxazolone monomer (VDM) with N,N-methylenebis(acrylamide) employed as a cross-linker to yield functional core cross-linked star polymers. Spermine was successfully attached to the star core by reaction with VDM. Finally, the secondary amine groups were reacted with NO gas to yield NO-core cross-linked star polymers. The core cross-linked star polymers were found to release NO in a controlled, slow delivery in bacterial cultures showing great efficacy in preventing both cell attachment and biofilm formation in Pseudomonas aeruginosa over time via a nontoxic mechanism, confining bacterial growth to the suspended liquid.
生物膜在人类传染病中发挥的主要作用日益受到认可，因为它们既能在活体组织上形成，也能在非生物表面形成，这对诸如可植入生物医学设备或导管等依赖于长时间与人体接触的应用具有严重影响。因此，迫切需要开发改良的疗法来有效根除不需要的生物膜。最近，生物信号分子一氧化氮（NO）被确定为生物膜中扩散事件的关键调节因子。在本文中，我们报道了一类新型的核心交联星形聚合物，其设计目的是以可控方式储存和释放一氧化氮，用于生物膜的分散。首先，通过可逆加成-断裂链转移聚合（RAFT）采用先臂法制备核心交联星形聚合物。通过RAFT聚合合成聚（低聚乙二醇甲氧基丙烯酸酯）链，然后在2-乙烯基-4,4-二甲基-5-恶唑酮单体（VDM）存在下，以N,N-亚甲基双丙烯酰胺作为交联剂进行扩链，得到功能性核心交联星形聚合物。通过与VDM反应，精胺成功连接到星形核心上。最后，仲胺基团与NO气体反应生成NO-核心交联星形聚合物。发现核心交联星形聚合物在细菌培养物中以可控、缓慢的方式释放NO，通过无毒机制随着时间的推移在预防铜绿假单胞菌的细胞附着和生物膜形成方面显示出巨大功效，将细菌生长限制在悬浮液中。
