Surface Charge Switchable Supramolecular Nanocarriers for Nitric Oxide Synergistic Photodynamic Eradication of Biofilms
Surface Charge Switchable Supramolecular Nanocarriers for Nitric Oxide Synergistic Photodynamic Eradication of Biofilms
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DOI：
10.1021/acsnano.9b05493
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发表时间：
2020-01-01
期刊：
影响因子：
17.1
通讯作者：
Ji, Jian
中科院分区：
文献类型：
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作者：
Hu, Dengfeng;Deng, Yongyan;Ji, Jian
生物膜已导致大量顽固性临床感染，对公众健康构成严重威胁。迫切需要开发原创的抗菌策略来根除生物膜。在此，我们开发了一种表面电荷可切换的超分子纳米载体，它表现出对酸性生物膜的pH响应性渗透，用于一氧化氮（NO）协同光动力消灭耐甲氧西林金黄色葡萄球菌（MRSA）生物膜，并且在激光照射下对健康组织的损害可以忽略不计。最初，通过主客体相互作用将谷胱甘肽（GSH）敏感的α-环糊精（α-CD）缀合一氧化氮（NO）前药（α-CD-NO）和二氢卟酚e6（Ce6）前药（α-CD-Ce6）整合到pH敏感的聚（乙二醇）（PEG）嵌段多肽共聚物（PEG-（KLAKLAK）（2）-DA）中，超分子纳米载体精心制备了α-CD-Ce6-NO-DA。超分子纳米载体显示出完全的表面电荷反转，从生理pH值（7.4）下的负电荷到酸性生物膜pH值（5.5）下的正电荷，促进有效渗透到生物膜中。一旦渗透到生物膜中，纳米载体就会在生物膜中过度表达的GSH触发下快速释放NO，不仅产生丰富的NO来杀死细菌，而且还可以降低生物膜GSH水平以提高光动力治疗（PDT）效率。另一方面，NO可以与活性氧（ROS）反应产生活性氮（RNS），进一步提高PDT效率。由于表面电荷可切换的GSH敏感NO纳米载体能够有效穿透生物膜并耗尽生物膜GSH，因此可以在低光敏剂剂量和激光强度下大大提高PDT效率，并且对健康组织造成的副作用可以忽略不计。考虑到上述优点，这项工作中开发的策略可能为对抗生物膜感染提供巨大的可能性。
Biofilm has resulted in numerous obstinate clinical infections, posing severe threats to public health. It is urgent to develop original antibacterial strategies for eradicating biofilms. Herein, we develop a surface charge switchable supramolecular nanocarrier exhibiting pH-responsive penetration into an acidic biofilm for nitric oxide (NO) synergistic photodynamic eradication of the methicillin-resistant Staphylococcus aureus (MRSA) biofilm with negligible damage to healthy tissues under laser irradiation. Originally, by integrating the glutathione (GSH)-sensitive alpha-cyclodextrin (alpha-CD) conjugated nitric oxide (NO) prodrug (alpha-CD-NO) and chlorin e6 (Ce6) prodrug (alpha-CD-Ce6) into the pH-sensitive poly(ethylene glycol) (PEG) block polypeptide copolymer (PEG-(KLAKLAK)(2)-DA) via host-guest interaction, the supramolecular nanocarrier alpha-CD-Ce6-NO-DA was finely prepared. The supramolecular nanocarrier shows complete surface charge reversal from negative charge at physiological pH (7.4) to positive charge at acidic biofilm pH (5.5), promoting efficient penetration into the biofilm. Once infiltrated into the biofilm, the nanocarrier exhibits rapid NO release triggered by the overexpressed GSH in the biofilm, which not only produces abundant NO for killing bacteria but also reduces the biofilm GSH level to improve photodynamic therapy (PDT) efficiency. On the other hand, NO can react with reactive oxygen species (ROS) to produce reactive nitrogen species (RNS), further improving the PDT efficiency. Due to the effective penetration into the biofilm and depletion of biofilm GSH, the surface charge switchable GSH-sensitive NO nanocarrier can greatly improve the PDT efficiency at a low photosensitizer dose and laser intensity and cause negligible side effect to healthy tissues. Considering the above advantages, the strategy developed in this work may offer great possibilities to fight against biofilm infections.