Self-Defensive Antimicrobial Surfaces Using Polymyxin-Loaded Poly(styrene sulfonate) Microgels
Self-Defensive Antimicrobial Surfaces Using Polymyxin-Loaded Poly(styrene sulfonate) Microgels
复制标题
使用负载多粘菌素的聚（苯乙烯磺酸盐）微凝胶的自我防御抗菌表面
DOI：
10.1021/acsbiomaterials.2c00783
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发表时间：
2022
影响因子：
5.8
通讯作者：
Libera, Matthew
中科院分区：
文献类型：
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作者：
Xiao, Xixi;Ji, Jingjing;Wang, Haoyu;Nangia, Shikha;Wang, Hongjun;Libera, Matthew
自我防御的抗微生物表面是令人感兴趣的，因为它们可以抑制细菌定植，同时在没有细菌挑战的情况下最小化不必要的抗微生物释放。一种自我防御的方法使用自组装，首先存款一层亚单层的微凝胶涂层，然后通过与小分子抗菌剂复合来装载这些微凝胶。微凝胶/抗微生物剂复合强度是控制抗微生物剂在暴露于介质时保持隔离在微凝胶内以及响应于细菌挑战而释放的能力的关键参数。在这里，我们研究了两种FDA批准的阳离子抗生素粘杆菌素（多粘菌素E）和多粘菌素B与聚（苯乙烯磺酸盐）（PSS）微凝胶的相对络合强度。这些多粘菌素是在pH 7.4下具有+5电荷的类似环状多肽。然而，多粘菌素B用芳香环取代粘菌素中的二甲基部分，这种芳香性可以通过π和疏水相互作用影响复合。粗粒分子动力学表明，与多粘菌素B/PSS复合相关的自由能变化比粘菌素/PSS复合相关的自由能变化更负。实验上，微凝胶去溶胀的原位光学显微镜显示，这两种抗生素从低离子强度磷酸盐缓冲液中快速加载。增强的多粘菌素B/PSS络合强度然后通过随后暴露于具有不同NaCl浓度的流动的无磷缓冲液来证明。负载有多粘菌素B的微凝胶比粘菌素/PSS微凝胶在更高的盐浓度下保持稳定的去溶胀。重要的是，将负载的微凝胶暴露于E。大肠杆菌素营养自由流动的磷酸盐缓冲液显示，细菌通过与负载的微凝胶的物理接触而被杀死，这与自我防御的接触转移机制一致。这些发现表明，基于FDA批准的抗生素的非代谢性细菌触发释放，在生理条件下创建有效的自我防御抗菌表面的途径。
Self-defensive antimicrobial surfaces are of interest because they can inhibit bacterial colonization while minimizing unnecessary antimicrobial release in the absence of a bacterial challenge. One self-defensive approach uses self-assembly to first deposit a submonolayer coating of polyelectrolyte microgels and subsequently load those microgels by complexation with small-molecule antimicrobials. The microgel/antimicrobial complexation strength is a key parameter that controls the ability of the antimicrobial both to remain sequestered within the microgels when exposed to medium and to release in response to a bacterial challenge. Here we study the relative complexation strengths of two FDA-approved cationic antibiotics─colistin (polymyxin E) and polymyxin B─with microgels of poly(styrene sulfonate) (PSS). These polymyxins are similar cyclic polypeptides with +5 charge at pH 7.4. However, polymyxin B substitutes an aromatic ring for a dimethyl moiety in colistin, and this aromaticity can influence complexation via π and hydrophobic interactions. Coarse-grained molecular dynamics shows that the free-energy change associated with polymyxin B/PSS complexation is more negative than that of colistin/PSS complexation. Experimentally,in situoptical microscopy of microgel deswelling shows that both antibiotics load quickly from low-ionic-strength phosphate buffer. The enhanced polymyxin B/PSS complexation strength is then manifested by subsequent exposure to flowing antibiotic-free buffer with varying NaCl concentration. Microgels loaded with polymyxin B remain stably deswollen to higher salt concentrations than do colistin/PSS microgels. Importantly, exposing loaded microgels toE. coliin nutrient-free-flowing phosphate buffer shows that bacteria are killed by physical contact with the loaded microgels consistent with the contact-transfer mechanism of self-defensiveness.In vitroculture experiments show that these same surfaces, nevertheless, support the adhesion, spreading and proliferation of human fetal osteoblasts. These findings suggest a pathway to create a self-defensive antimicrobial surface effective under physiological conditions based on the nonmetabolic bacteria-triggered release of FDA-approved antibiotics.