含银介孔二氧化硅纳米粒子作为新型抗结核分枝杆菌药物的研究
Mesoporous silica nanoparticles containing silver as novel antimycobacterial agents against Mycobacterium tuberculosis
摘要：
结核病今天仍然是一个主要的公共卫生问题，每年共有900万新病例和200万死亡病例。由于缺乏有效的疫苗以及对抗生素高度耐药的结核分枝杆菌（Mtb）新菌株的不断出现，预计在不久的将来会出现复杂的情况。使用纳米颗粒作为抗生素的替代品来解决这个问题，因为它们在耐药菌株中具有潜在的有效性。在这种情况下，银纳米颗粒已经显示出高杀菌功效，尽管它们的使用受到其相对高的毒性的限制，这要求设计允许基于银的纳米颗粒安全地递送到靶细胞或组织的纳米载体。在这项工作中，介孔二氧化硅纳米粒子被用作载体的基于银的纳米粒子作为抗结核分枝杆菌的抗分枝杆菌剂。两种不同的合成方法已被用来提供，一方面，一个二维六方介孔二氧化硅纳米系统，其中包含分布在整个二氧化硅网络的溴化银纳米粒子，另一方面，一个核@壳纳米系统与金属银纳米粒子作为核和介孔二氧化硅壳在径向介孔重排。两种材料在使用Mtb的体外试验中均表现出良好的抗分枝杆菌能力，低于含有溴化银的纳米系统的最小抑制浓度。因此，已通过冷冻电子显微镜研究了该材料与分枝杆菌细胞的相互作用，建立了观察到的抗杀菌作用与细胞包膜中诱导的损伤之间的直接联系。
英文摘要：
Tuberculosis remains today a major public health issue with a total of 9 million new cases and 2 million deaths annually. The lack of an effective vaccine and the increasing emergence of new strains of Mycobacterium tuberculosis (Mtb) highly resistant to antibiotics, anticipate a complicated scenario in the near future. The use of nanoparticles features as an alternative to antibiotics in tackling this problem due to their potential effectiveness in resistant bacterial strains. In this context, silver nanoparticles have demonstrated high bactericidal efficacy, although their use is limited by their relatively high toxicity, which calls for the design of nanocarriers that allow silver based nanoparticles to be safely delivered to the target cells or tissues. In this work mesoporous silica nanoparticles are used as carriers of silver based nanoparticles as antimycobacterial agent against Mtb. Two different synthetic approaches have been used to afford, on the one hand, a 2D hexagonal mesoporous silica nanosystem which contains silver bromide nanoparticles distributed all through the silica network and, on the other hand, a core@shell nanosystem with metallic silver nanoparticles as core and mesoporous silica shell in a radial mesoporous rearrangement. Both materials have demonstrated good antimycobacterial capacity in in vitro test using Mtb, being lower the minimum inhibitory concentration for the nanosystem which contains silver bromide. Therefore, the interaction of this material with the mycobacterial cell has been studied by cryo-electron microscopy, establishing a direct connection between the antimycobactericidal effect observed and the damage induced in the cell envelope.
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