Nanosome-Mediated Delivery Of Hdac Inhibitors and Oxygen Molecules for the Transcriptional Reactivation of Latent Hiv-Infected Cd4 + T Cells

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 in...

Full description

Saved in:
Bibliographic Details
Published in:Small (Weinheim an der Bergstrasse, Germany) Germany), 2023-09, Vol.19 (37), p.e2301730-e2301730
Main 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
Format: Article
Language:English
Subjects:
Bilayers
Binding
Drug carriers
Drug delivery systems
HIV
Human immunodeficiency virus
Inhibitors
Lymphocytes
Nanotechnology
Oxygen
Peptides
Phospholipids
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1613-6810
1613-6829
DOI:10.1002/smll.202301730