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靶向 HIV-1 潜伏细胞的药物传递系统以实现病毒清除

Drug Delivery System Targeting CD4 T Cells for HIV-1 Latency Reactivation Towards the Viral Eradication.

机构信息

Graduate Program in Biotechnology, The Graduate School, Chiang Mai University, Chiang Mai, Thailand; Faculty of Science, Department of Chemistry, Division of Biochemistry and Biochemical Technology, Chiang Mai University, Chiang Mai, Thailand.

Faculty of Science, Department of Chemistry, Division of Biochemistry and Biochemical Technology, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Materials Science and Technology, Chiang Mai University, 239 Huay Kaew Road, Chiang Mai 50200, Thailand.

出版信息

J Pharm Sci. 2020 Oct;109(10):3013-3020. doi: 10.1016/j.xphs.2020.06.019. Epub 2020 Jun 25.

Abstract

Development of a cure for HIV/AIDS has been a great challenge due to the establishment of the HIV-1 viral reservoir, mainly within resting CD4 memory T cells. As a step towards a cure for HIV, this study aimed to develop an approach that reactivates HIV-1 latently infected cells by employing a drug delivery system using immunoliposomes targeting CD4 T cells. The immunoliposomes were examined for physicochemical properties and determined for their potential stability. A histone deacetylase (HDAC) inhibitor SAHA was used as a model drug being encapsulated within the immunoliposomes that are conjugated with anti-CD4 antibodies. The immunoliposomes are effectively and specifically taken up by the CD4 J-Lat 10.6 cells, and significantly less so by the CD4 ACH-2 cells. For HIV-1 latent cell reactivation, SAHA-encapsulated immunoliposomes (SAHA-IL) and SAHA-encapsulated liposomes (SAHA-LP) can reactivate HIV latency as effectively as SAHA compound alone. Additionally, a combination of SAHA-IL and a protein kinase C activator, bryostatin-1, also exhibits a synergistic effect on the reactivation. The developed system thus presents a viable option to become a promising approach for HIV-1 latency reversing treatment, a strategy towards developing a functional cure for HIV.

摘要

由于 HIV-1 病毒库的建立,主要是在静止的 CD4 记忆 T 细胞内,开发治愈 HIV/AIDS 的方法一直是一个巨大的挑战。作为治愈 HIV 的一个步骤,本研究旨在开发一种通过使用针对 CD4 T 细胞的免疫脂质体药物递送系统来激活潜伏感染细胞的方法。研究了免疫脂质体的理化性质,并确定了它们的潜在稳定性。组蛋白去乙酰化酶 (HDAC) 抑制剂 SAHA 被用作模型药物,被包裹在与抗 CD4 抗体偶联的免疫脂质体中。免疫脂质体有效地、特异性地被 CD4 J-Lat 10.6 细胞摄取,而被 CD4 ACH-2 细胞摄取的则少得多。为了激活潜伏的 HIV-1 细胞,包载 SAHA 的免疫脂质体 (SAHA-IL) 和包载 SAHA 的脂质体 (SAHA-LP) 可以像单独的 SAHA 化合物一样有效地激活 HIV 潜伏。此外,SAHA-IL 与蛋白激酶 C 激活剂 bryostatin-1 的联合使用也对再激活表现出协同作用。因此,所开发的系统为 HIV-1 潜伏逆转治疗提供了一种可行的选择,是开发 HIV 功能性治愈策略的一种有前途的方法。

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