TY - JOUR
T1 - Peptide self-assembly nanoparticles loaded with panobinostat to activate latent human immunodeficiency virus
AU - Kuai, Qiyuan
AU - Wang, Yu
AU - Gao, Fenghua
AU - Qi, Yingqiu
AU - Wang, Rui
AU - Wang, Yanbing
AU - Lu, Xiaofan
AU - Zhao, Ying
AU - Nie, Guangjun
AU - He, Min
AU - Zhou, Hong
AU - Jiang, Xingwei
AU - Ren, Suping
AU - Yu, Qun
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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.
KW - HIV reservoir
KW - Histone deacetylase inhibitors
KW - Latent HIV
KW - Nanoparticles
KW - Panobinostat
KW - Peptide self-assembly
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UR - http://www.scopus.com/inward/citedby.url?scp=85063261470&partnerID=8YFLogxK
U2 - 10.1166/jbn.2019.2764
DO - 10.1166/jbn.2019.2764
M3 - Article
C2 - 30890229
AN - SCOPUS:85063261470
VL - 15
SP - 979
EP - 992
JO - Journal of Biomedical Nanotechnology
JF - Journal of Biomedical Nanotechnology
SN - 1550-7033
IS - 5
ER -