TY - JOUR
T1 - RVG Peptide-Functionalized Favipiravir Nanoparticle Delivery System Facilitates Antiviral Therapy of Neurotropic Virus Infection in a Mouse Model
AU - Ren, Meishen
AU - Zhou, You
AU - Tu, Teng
AU - Jiang, Dike
AU - Pang, Maonan
AU - Li, Yanwei
AU - Luo, Yan
AU - Yao, Xueping
AU - Yang, Zexiao
AU - Wang, Yin
N1 - This research was funded by the Provincial Natural Science Foundation of Sichuan (2023NS-FSC1216); The China Postdoctoral Science Foundation (2022M722300); The Hong Kong Scholars Program 2022, China Postdoctoral Science Foundation (XJ2022047); The Sichuan Province Science and Technology Planning Program (2021ZDZX0010).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/3/19
Y1 - 2023/3/19
N2 - Neurotropic viruses severely damage the central nervous system (CNS) and
human health. Common neurotropic viruses include rabies virus (RABV),
Zika virus, and poliovirus. When treating neurotropic virus infection,
obstruction of the blood–brain barrier (BBB) reduces the efficiency of
drug delivery to the CNS. An efficient intracerebral delivery system can
significantly increase intracerebral delivery efficiency and facilitate
antiviral therapy. In this study, a rabies virus glycopeptide (RVG)
functionalized mesoporous silica nanoparticle (MSN) packaging
favipiravir (T-705) was developed to generate T-705@MSN-RVG. It was
further evaluated for drug delivery and antiviral treatment in a
VSV-infected mouse model. The RVG, a polypeptide consisting of 29 amino
acids, was conjugated on the nanoparticle to enhance CNS delivery. The
T-705@MSN-RVG caused a significant decrease in virus titers and virus
proliferation without inducing substantial cell damage in vitro. By
releasing T-705, the nanoparticle promoted viral inhibition in the brain
during infection. At 21 days post-infection (dpi), a significantly
enhanced survival ratio (77%) was observed in the group inoculated with
nanoparticle compared with the non-treated group (23%). The viral RNA
levels were also decreased in the therapy group at 4 and 6 dpi compared
with that of the control group. The T-705@MSN-RVG could be considered a
promising system for CNS delivery for treating neurotropic virus
infection
AB - Neurotropic viruses severely damage the central nervous system (CNS) and
human health. Common neurotropic viruses include rabies virus (RABV),
Zika virus, and poliovirus. When treating neurotropic virus infection,
obstruction of the blood–brain barrier (BBB) reduces the efficiency of
drug delivery to the CNS. An efficient intracerebral delivery system can
significantly increase intracerebral delivery efficiency and facilitate
antiviral therapy. In this study, a rabies virus glycopeptide (RVG)
functionalized mesoporous silica nanoparticle (MSN) packaging
favipiravir (T-705) was developed to generate T-705@MSN-RVG. It was
further evaluated for drug delivery and antiviral treatment in a
VSV-infected mouse model. The RVG, a polypeptide consisting of 29 amino
acids, was conjugated on the nanoparticle to enhance CNS delivery. The
T-705@MSN-RVG caused a significant decrease in virus titers and virus
proliferation without inducing substantial cell damage in vitro. By
releasing T-705, the nanoparticle promoted viral inhibition in the brain
during infection. At 21 days post-infection (dpi), a significantly
enhanced survival ratio (77%) was observed in the group inoculated with
nanoparticle compared with the non-treated group (23%). The viral RNA
levels were also decreased in the therapy group at 4 and 6 dpi compared
with that of the control group. The T-705@MSN-RVG could be considered a
promising system for CNS delivery for treating neurotropic virus
infection
KW - antiviral therapy of neurotropic virus infection
KW - drug CNS delivery
KW - favipiravir
UR - http://www.scopus.com/inward/record.url?scp=85151109716&partnerID=8YFLogxK
U2 - 10.3390/ijms24065851
DO - 10.3390/ijms24065851
M3 - Journal article
C2 - 36982925
AN - SCOPUS:85151109716
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 6
M1 - 5851
ER -
