Highly active antiretroviral therapy (HAART) can turn human immunodeficiency virus-1 (HIV-1) infection into a controllable chronic disease, but because of the presence of an HIV reservoir, it cannot completely eliminate the virus in HIV-infected patients. The activation of latent reservoirs is the key to the successful treatment of acquired immune deficiency syndrome (AIDS). As a class of latency-reversing agents (LRAs), histone deacetylase inhibitors (HDACis), such as panobinostat, have been the most widely investigated, but most of them have resulted in only a modest and transient activation of HIV latency. To improve the potency of latency activation, an injectable peptide self-assembly nanoparticle loaded with panobinostat (PNP-P) was designed with the ability to efficiently penetrate the cell to achieve better drug delivery and activation of latent HIV. The results confirmed that these nanoparticles could activate latently infected cells in vitro and in vivo and activate peripheral blood mononuclear cells (PBMCs) from latently infected patients ex vivo. Increased cellular drug uptake made the PNP-P more effective than panobinostat alone. Therefore, this strategy demonstrates that nanotechnology can help improve the activation of latent HIV, and this study lays a foundation for further development of LRA delivery systems for use against an HIV reservoir.

中文翻译：

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负载Panobinostat的肽自组装纳米颗粒可激活潜在的人类免疫缺陷病毒。

高效的抗逆转录病毒疗法（HAART）可以将人类免疫缺陷病毒1（HIV-1）感染转变为可控制的慢性疾病，但是由于存在HIV储备库，因此无法完全消除HIV感染患者中的病毒。潜伏水库的激活是成功治疗获得性免疫缺陷综合症（AIDS）的关键。作为一类潜伏期逆转剂（LRA），组蛋白脱乙酰基酶抑制剂（HDACis）（例如panobinostat）已得到最广泛的研究，但其中大多数仅导致了适度和短暂的HIV潜伏期激活。为了提高延迟激活的效力，设计了一种载有panobinostat（PNP-P）的可注射肽自组装纳米颗粒，该颗粒具有有效渗透细胞以实现更好的药物递送和潜在HIV活化的能力。结果证实这些纳米粒子可以激活潜伏感染的细胞在体外和在体内和从激活潜伏感染的病人的外周血单核细胞（PBMC）在体外。细胞药物吸收的增加使PNP-P比单独的panobinostat更有效。因此，该策略表明纳米技术可以帮助改善潜在的HIV激活，这项研究为进一步开发用于HIV储存库的LRA递送系统奠定了基础。