Ga(III) Nanoparticles Inhibit Growth of both Mycobacterium tuberculosis and HIV and Release of Interleukin-6 (IL-6) and IL-8 in Coinfected Macrophages.
Ga(III) Nanoparticles Inhibit Growth of both Mycobacterium tuberculosis and HIV and Release of Interleukin-6 (IL-6) and IL-8 in Coinfected Macrophages.
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DOI：
10.1128/aac.02505-16
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发表时间：
2017-04
影响因子：
4.9
通讯作者：
Narayanasamy P
中科院分区：
文献类型：
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作者：
Choi SR;Britigan BE;Narayanasamy P
由于长期的治疗要求、药物毒性和耐药性的出现，1型人类免疫缺陷病毒（HIV）和结核分枝杆菌合并感染的个体的治疗具有挑战性。单核巨噬细胞是HIV和M.结核在这里，艾滋病毒和M。通过用MP靶向的镓（Ga）纳米颗粒预加载人巨噬细胞以限制随后的HIV和M的同时感染来研究结核病合并感染。结核Ga纳米颗粒提供了持续15天的药物释放，并显着抑制HIV和M的复制。结核将Ga纳米颗粒添加到已经感染M.结核病或HIV的感染导致这些感染的程度显著降低，但程度小于用MP的纳米颗粒预加载实现的程度。此外，HIV和M.结核病的小鼠和装载有Ga纳米颗粒的小鼠在药物装载后降低白细胞介素-6（IL-6）和IL-8分泌水平长达15天。Ga纳米颗粒还降低了离子霉素和脂多糖诱导的巨噬细胞分泌IL-6和IL-8的水平，这可能是通过调节IκB激酶-β/NF-κB途径实现的。将Ga纳米颗粒递送到巨噬细胞是抑制HIV和M的有效长效方法。结核病合并感染的巨噬细胞在体外，并设置了阶段的发展，新的方法来治疗这些重要的感染。
Treatment of individuals coinfected with human immunodeficiency virus (HIV) type 1 and Mycobacterium tuberculosis is challenging due to the prolonged treatment requirements, drug toxicity, and emergence of drug resistance. Mononuclear phagocytes (MP; macrophages) are one of the natural reservoirs for both HIV and M. tuberculosis. Here, the treatment of HIV and M. tuberculosis coinfection was studied by preloading human macrophages with MP-targeted gallium (Ga) nanoparticles to limit subsequent simultaneous infection with both HIV and M. tuberculosis. Ga nanoparticles provided sustained drug release for 15 days and significantly inhibited the replication of both HIV and M. tuberculosis. Addition of Ga nanoparticles to MP already infected with M. tuberculosis or HIV resulted in a significant decrease in the magnitude of these infections, but the magnitude was less than that achieved with nanoparticle preloading of the MP. In addition, macrophages that were coinfected with HIV and M. tuberculosis and that were loaded with Ga nanoparticles reduced the levels of interleukin-6 (IL-6) and IL-8 secretion for up to 15 days after drug loading. Ga nanoparticles also reduced the levels of IL-6 and IL-8 secretion by ionomycin- and lipopolysaccharide-induced macrophages, likely by modulating the IκB kinase-β/NF-κB pathway. Delivery of Ga nanoparticles to macrophages is a potent long-acting approach for suppressing HIV and M. tuberculosis coinfection of macrophages in vitro and sets the stage for the development of new approaches to the treatment of these important infections.