Choi Seoung-Ryoung, Britigan Bradley E, Narayanasamy Prabagaran
Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Antimicrob Agents Chemother. 2017 Mar 24;61(4). doi: 10.1128/AAC.02505-16. Print 2017 Apr.
Treatment of individuals coinfected with human immunodeficiency virus (HIV) type 1 and 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 Here, the treatment of HIV and coinfection was studied by preloading human macrophages with MP-targeted gallium (Ga) nanoparticles to limit subsequent simultaneous infection with both HIV and Ga nanoparticles provided sustained drug release for 15 days and significantly inhibited the replication of both HIV and Addition of Ga nanoparticles to MP already infected with 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 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 coinfection of macrophages and sets the stage for the development of new approaches to the treatment of these important infections.
由于治疗时间长、药物毒性以及耐药性的出现，同时感染1型人类免疫缺陷病毒（HIV）和[此处原文缺失病原体名称]的个体的治疗具有挑战性。单核吞噬细胞（MP；巨噬细胞）是HIV和[此处原文缺失病原体名称]的天然储存库之一。在此，通过用靶向MP的镓（Ga）纳米颗粒预加载人类巨噬细胞来研究HIV和[此处原文缺失病原体名称]合并感染的治疗，以限制随后同时感染HIV和[此处原文缺失病原体名称]。Ga纳米颗粒提供了15天的持续药物释放，并显著抑制了HIV和[此处原文缺失病原体名称]的复制。向已感染[此处原文缺失病原体名称]或HIV的MP中添加Ga纳米颗粒导致这些感染的程度显著降低，但降低程度小于对MP进行纳米颗粒预加载所达到的程度。此外，同时感染HIV和[此处原文缺失病原体名称]并加载了Ga纳米颗粒的巨噬细胞在药物加载后长达15天内降低了白细胞介素-6（IL-6）和IL-8的分泌水平。Ga纳米颗粒还可能通过调节IκB激酶-β/核因子κB（NF-κB）途径降低了离子霉素和脂多糖诱导的巨噬细胞中IL-6和IL-8的分泌水平。将Ga纳米颗粒递送至巨噬细胞是一种抑制巨噬细胞HIV和[此处原文缺失病原体名称]合并感染的有效长效方法，并为开发治疗这些重要感染的新方法奠定了基础。
