PLGA-PEG Nanoparticles Coated with Anti-CD45RO and Loaded with HDAC Plus Protease Inhibitors Activate Latent HIV and Inhibit Viral Spread.
Activating HIV-1 proviruses in latent reservoirs combined with inhibiting viral spread might be an effective anti-HIV therapeutic strategy. Active specific delivery of therapeutic drugs into cells harboring latent HIV, without the use of viral vectors, is a critical challenge to this objective. In this study, nanoparticles of poly(lactic-co-glycolic acid)-polyethylene glycol diblock copolymers conjugated with anti-CD45RO antibody and loaded with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and/or protease inhibitor nelfinavir (Nel) were tested for activity against latent virus in vitro. Nanoparticles loaded with SAHA, Nel, and SAHA + Nel were characterized in terms of size, surface morphology, zeta potential, entrapment efficiency, drug release, and toxicity to ACH-2 cells. We show that SAHA- and SAHA + Nel-loaded nanoparticles can target latently infected CD4(+) T-cells and stimulate virus production. Moreover, nanoparticles loaded with SAHA + NEL were capable of both activating latent virus and inhibiting viral spread. Taken together, these data demonstrate the potential of this novel reagent for targeting and eliminating latent HIV reservoirs.
Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science and Technology, Huainan, 232001, China.|The State Key Laboratory of Virology, Life Sciences College, Wuhan University, Wuhan, 430072, China.
Xiaolong
X
Tang
Clinical Laboratory, The Affiliated Huai'an Hospital of Xuzhou Medical College, Huai'an, 223002, China.
Yong
Y
Liang
Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science and Technology, Huainan, 232001, China.
Xinkuang
X
Liu
Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science and Technology, Huainan, 232001, China.
Shuping
S
Zhou
Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science and Technology, Huainan, 232001, China.
Liang
L
Liu
Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science and Technology, Huainan, 232001, China.
Fujina
F
Zhang
School of Biotechnology, Southern Medical University, Guangzhou, 510515, China.
Chunmei
C
Xie
Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science and Technology, Huainan, 232001, China.
Shuyu
S
Cai
Huainan First People's Hospital and First Affiliated Hospital of Medical College, Anhui University of Science and Technology, Huainan, 232001, China.
Jia
J
Wei
Department of Medical Genetics, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China. zyq666999@aliyun.com.
Yongqiang
Y
Zhu
The State Key Laboratory of Virology, Life Sciences College, Wuhan University, Wuhan, 430072, China. houwei@whu.edu.cn.
Wei
W
Hou
CD45RO; HIV-1; Memory T cells; Nanoparticles