Enzyme-Responsive Mesoporous Ruthenium for Combined Chemo-Photothermal Therapy of Drug-Resistant Bacteria
Enzyme-Responsive Mesoporous Ruthenium for Combined Chemo-Photothermal Therapy of Drug-Resistant Bacteria
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用于耐药细菌化疗光热联合治疗的酶响应介孔钌
DOI：
10.1021/acsami.9b07866
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发表时间：
2019
影响因子：
9.5
通讯作者：
Liu Jie
中科院分区：
文献类型：
--
作者：
Liu Yanan;Lin Ange;Liu Jiawei;Chen Xu;Zhu Xufeng;Gong Youcong;Yuan Guanglong;Chen Lanmei;Liu Jie
耐药菌的快速突变和新型抗生素研发的严重滞后使得新型抗菌药物的研究成为必然。具有独特尺寸效应和抗菌机制的纳米材料可以作为抗生素的替代品，因为它们产生耐药细菌的可能性很低。在这里，提出了一种具有协同化学光热治疗功能的酶响应纳米系统 AA@Ru@HA-MoS2 来治疗细菌感染。介孔钌纳米粒子（Ru NPs）被用作纳米载体，负载前药抗坏血酸（AA）并被透明质酸（HA）封装。然后，使用预涂有环丙沙星的二硫化钼（MoS2）作为具有靶向作用的催化剂与外表面结合。当纳米系统聚集在感染部位时，细菌分泌的Hyal可以降解HA封端并引发AA的释放，然后在MoS2的催化下原位产生羟基自由基（·OH）。此外，利用Ru纳米粒子良好的光热性能，可以实现化学光热联合抗菌治疗。该纳米系统对耐药革兰氏阳性和革兰氏阴性细菌表现出有效的杀菌活性。此外，它可以分解生物膜，抑制所含细菌，并防止新生物膜的形成。体内细菌感染模型也被证明可以加速伤口愈合。该研究表明 AA@Ru@HA-MoS2 作为新型酶响应纳米系统对抗耐药细菌感染的巨大潜力。
The rapid mutation of drug-resistant bacteria and the serious lag of development of new antibiotics necessitate research on novel antibacterial agents. Nanomaterials with unique size effect and antibacterial mechanism could serve as an alternative for antibiotics, since they showed low possibility to develop drug-resistant bacteria. Here, an enzyme-responsive nanosystem, AA@Ru@HA-MoS2, with a synergistic chemo-photothermal therapy function is proposed to treat bacterial infections. Mesoporous ruthenium nanoparticles (Ru NPs) were used as nanocarriers, loading prodrug ascorbic acid (AA) and encapsulated by hyaluronic acid (HA). Then, molybdenum disulfide (MoS2) precoated with ciprofloxacin was used as a catalyst with targeting effect binding to the outer surface. When the nanosystem gathered at the infection site, Hyal secreted by bacteria could degrade the HA capping and trigger the release of AA and then generated hydroxyl radicals (•OH) in situ by the catalysis of MoS2. In addition, taking advantage of the good photothermal property of Ru NPs, combined chemo-photothermal antibacterial therapy could be achieved. The nanosystem exhibited potent bactericidal activity against drug-resistant Gram-positive and Gram-negative bacteria. Furthermore, it could break down the biofilm, inhibit the contained bacteria, and prevent the formation of a new biofilm. The in vivo bacterium-infected model also proved accelerated wound healing. The study showed a high potential of AA@Ru@HA-MoS2as a novel enzyme-responsive nanosystem for combating drug-resistant bacterial infection.