Macrophage-Targeted Isoniazid-Selenium Nanoparticles Promote Antimicrobial Immunity and Synergize Bactericidal Destruction of Tuberculosis Bacilli
Macrophage-Targeted Isoniazid-Selenium Nanoparticles Promote Antimicrobial Immunity and Synergize Bactericidal Destruction of Tuberculosis Bacilli
复制标题
巨噬细胞靶向异烟肼硒纳米粒促进抗菌免疫并协同杀菌破坏结核杆菌
DOI：
10.1002/anie.201912122
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发表时间：
2020-01-16
影响因子：
16.6
通讯作者：
Chen, Zheng W.
中科院分区：
文献类型：
--
作者：
Pi, Jiang;Shen, Ling;Chen, Zheng W.
结核病(TB)的致病标志是结核分枝杆菌(Mtb)逃避吞噬小体破坏和有限的药物输送到受感染的细胞。几种纳米材料可以被包裹在溶酶体中，但开发功能纳米材料来促进吞噬溶酶体Mtb的清除仍然是一个巨大的挑战。在这里，我们报道了硒纳米颗粒(Se NPs)对结核分枝杆菌的杀菌作用，并进一步介绍了一种新的纳米材料辅助抗结核策略，该策略操纵Ison@Man-Se纳米颗粒协同药物诱导和吞噬作用破坏结核分枝杆菌。ISON@Man-Se纳米粒优先进入巨噬细胞，并在释放异烟肼的溶酶体中蓄积。令人惊讶的是，Ison@Man-Se/Man-Se纳米粒进一步促进了Mtb与溶酶体的融合，从而协同溶酶体和异烟肼对Mtb的破坏。同时，Ison@Man-Se/Man-Se NPs还诱导Mtb的自噬隔离，演变为与ROS-线粒体和PI3K/Akt/mTor信号通路有关的溶酶体相关的自噬Mtb降解。这种新的纳米材料辅助抗结核策略操纵抗微生物免疫和结核分枝杆菌清除，可能会潜在地服务于更有效的结核病和耐药结核病的治疗。
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.