Peptide self-assembly nanoparticles loaded with panobinostat to activate latent human immunodeficiency virus

Qiyuan Kuai, Yu Wang, Fenghua Gao, Yingqiu Qi, Rui Wang, Yanbing Wang, Xiaofan Lu, Ying Zhao, Guangjun Nie, Min He, Hong Zhou, Xingwei Jiang, Suping Ren, Qun Yu

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)979-992
Number of pages14
JournalJournal of Biomedical Nanotechnology
Volume15
Issue number5
DOIs
StatePublished - May 2019

Keywords

  • HIV reservoir
  • Histone deacetylase inhibitors
  • Latent HIV
  • Nanoparticles
  • Panobinostat
  • Peptide self-assembly

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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