Nanosome-Mediated Delivery Of Hdac Inhibitors and Oxygen Molecules for the Transcriptional Reactivation of Latent Hiv-Infected Cd4+ T Cells
- Authors
- Hong, Joohye; Choi, Yonghyun; Lee, Gahyun; Kim, Jiwon; Jang, Yeonwoo; Yoon, Cheol-Hee; Seo, Hyun Wook; Park, In-Kyu; Kang, Shin Hyuk; Choi, Jonghoon
- Issue Date
- Sep-2023
- Publisher
- John Wiley and Sons Inc
- Keywords
- CD4 <sup>+</sup> T cells; CXCR4; drug delivery; histone deacetylase (HDAC) inhibitors; human immunodeficiency virus (HIV); liposome; oxygen delivery; shock-and-kill
- Citation
- Small, v.19, no.37
- Journal Title
- Small
- Volume
- 19
- Number
- 37
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/67603
- DOI
- 10.1002/smll.202301730
- ISSN
- 1613-6810
1613-6829
- Abstract
- The treatment of human immunodeficiency virus (HIV) infection is notoriously difficult due to the ability of this virus to remain latent in the host's CD4+ T cells. Histone deacetylases (HDACs) interfere with DNA transcription in HIV-infected hosts, resulting in viral latency. Therefore, HDAC inhibitors can be used to activate viral transcription in latently infected cells, after which the virus can be eliminated through a shock-and-kill strategy. Here, a drug delivery system is developed to effectively deliver HDAC inhibitors to latent HIV-infected cells. Given that the efficacy of HDAC inhibitors is reduced under hypoxic conditions, oxygen-containing nanosomes are used as drug carriers. Oxygen-containing nanosomes can improve the efficiency of chemotherapy by delivering essential oxygen to cells. Additionally, their phospholipid bilayer structure makes them uniquely well-suited for drug delivery. In this study, a novel drug delivery system is developed by taking advantage of the oxygen carriers in these oxygen nanosomes, incorporating a multi-drug strategy consisting of HDAC inhibitors and PKA activators, and introducing CXCR4 binding peptides to specifically target CD4+ T cells. Oxygen nanosomes with enhanced targeting capability through the introduction of the CXCR4 binding peptide mitigate drug toxicity and slow down drug release. The observed changes in the expression of p24, a capsid protein of HIV, indirectly confirm that the proposed drug delivery system can effectively induce transcriptional reactivation of HIV in latent HIV-infected cells. © 2023 Wiley-VCH GmbH.
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