Pathogenesis hallmarks for tuberculosis (TB) are the Mycobacterium tuberculosis (Mtb) escape from phagolysosomal destruction and limited drug delivery into infected cells. Several nanomaterials can be entrapped in lysosomes, but the development of functional nanomaterials to promote phagolysosomal Mtb clearance remains a big challenge. Here, we report on the bactericidal effects of selenium nanoparticles (Se NPs) against Mtb and further introduce a novel nanomaterial-assisted anti-TB strategy manipulating Ison@Man-Se NPs for synergistic drug-induced and phagolysosomal destruction of Mtb. Ison@Man-Se NPs preferentially entered macrophages and accumulated in lysosomes releasing Isoniazid. Surprisingly, Ison@Man-Se/Man-Se NPs further promoted the fusion of Mtb into lysosomes for synergistic lysosomal and Isoniazid destruction of Mtb. Concurrently, Ison@Man-Se/Man-Se NPs also induced autophagy sequestration of Mtb, evolving into lysosome-associated autophagosomal Mtb degradation linked to ROS-mitochondrial and PI3K/Akt/mTOR signaling pathways. This novel nanomaterial-assisted anti-TB strategy manipulating antimicrobial immunity and Mtb clearance may potentially serve in more effective therapeutics against TB and drug-resistant TB.

中文翻译：

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靶向巨噬细胞的异烟肼硒纳米颗粒可提高抗菌素的免疫力，并协同杀灭结核杆菌。

结核病（TB）的发病机理标志是结核分枝杆菌（Mtb）从吞噬溶酶体破坏中逃逸，并且药物向感染细胞的传递受到限制。几种纳米材料可以包裹在溶酶体中，但是开发功能性纳米材料以促进吞噬体Mtb清除仍然是一个巨大的挑战。在这里，我们报道硒纳米粒子（Se NPs）对Mtb的杀菌作用，并进一步介绍了一种新型的纳米材料辅助抗结核策略，该策略可操纵Ison @ Man-Se NPs协同作用，诱导药物诱导的和吞噬性的Mtb破坏。Ison @ Man-Se NPs优先进入巨噬细胞并积累在溶酶体中，释放异烟肼。出人意料的是，Ison @ Man-Se / Man-Se NP进一步促进了Mtb融合到溶酶体中，从而协同破坏了Mtb的溶酶体和异烟肼。同时，Ison @ Man-Se / Man-Se NPs也诱导了Mtb的自噬螯合，发展为与ROS线粒体和PI3K / Akt / mTOR信号通路相关的溶酶体相关自噬体Mtb降解。这种新颖的纳米材料辅助的抗结核策略，可控制抗菌素的免疫力和清除Mtb的潜力，可能会在针对结核病和耐药结核病的更有效治疗方法中发挥作用。