Affiliation: | 1. School of Integrative Engineering, Chung-Ang University, Seoul, 06974 Republic of Korea;2. School of Integrative Engineering, Chung-Ang University, Seoul, 06974 Republic of Korea Feynman Institute of Technology, Nanomedicine Corporation, Seoul, 06974 Republic of Korea;3. Division of Chronic Viral Disease, Center for Emerging Virus Research, National Institute of Health, Cheongju, 28159 Republic of Korea;4. Department of Biomedical Sciences, Chonnam National University Medical School, 160 Baekseo-ro, Gwangju, 58128 Republic of Korea;5. Departments of Plastic and Reconstructive Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, 06973 Republic of Korea |
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. |