A multifunctional nanoparticle as a prophylactic and therapeutic approach targeting respiratory syncytial virus

Eleni Markoutsa; Andrew R McGill; Anthony Singer; Heta Jadhav; Subhra Mohapatra; Shyam S Mohapatra

doi:10.1016/j.nano.2020.102325

A multifunctional nanoparticle as a prophylactic and therapeutic approach targeting respiratory syncytial virus

Nanomedicine. 2021 Feb:32:102325. doi: 10.1016/j.nano.2020.102325. Epub 2020 Nov 10.

Authors

Eleni Markoutsa¹, Andrew R McGill², Anthony Singer³, Heta Jadhav³, Subhra Mohapatra⁴, Shyam S Mohapatra⁵

Affiliations

¹ James A Haley VA Hospital, Tampa, FL, USA; Center for Research and Education in Nanobio-engineering, Department of Internal Medicine, University of South Florida, Tampa, FL, USA; College of Pharmacy Graduate Programs, University of South Florida, Tampa, FL, USA.
² James A Haley VA Hospital, Tampa, FL, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL, USA.
³ College of Pharmacy Graduate Programs, University of South Florida, Tampa, FL, USA.
⁴ James A Haley VA Hospital, Tampa, FL, USA; Center for Research and Education in Nanobio-engineering, Department of Internal Medicine, University of South Florida, Tampa, FL, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL, USA.
⁵ James A Haley VA Hospital, Tampa, FL, USA; Center for Research and Education in Nanobio-engineering, Department of Internal Medicine, University of South Florida, Tampa, FL, USA; College of Pharmacy Graduate Programs, University of South Florida, Tampa, FL, USA. Electronic address: smohapat@usf.edu.

PMID: 33186695
DOI: 10.1016/j.nano.2020.102325

Abstract

Respiratory Syncytial Virus (RSV) has been a major health concern globally for decades, yet no effective prophylactic or treatment regimen is available. The key viral proteins responsible for RSV pathology include the fusion protein (F), the immunomodulatory non-structural-protein 1 (NS1) and the phosphoprotein (P) involved in viral replication. Herein, we developed a novel shell-core multifunctional nanosystem with dual payload: a plasmid construct encoding for shRNAs against NS1 and P, and an anti-fusion peptide (HR2D). Anti-ICAM1 antibody conjugated on the nanoparticle (NP) surface is used to target RSV infected cells. Our data show the potential of this nanosystem as a prophylactic and/or a therapeutic regimen against RSV infection. Furthermore, therapy of RSV infected mice with this nanosystem, in addition to reducing viral load, modulated expression of Th2 and allergy-associated cytokines such as IL4, IL-13 and IL-17 indicating a direct role of this nanosystem in the mechanisms involved in the immunoregulation of disease pathogenesis.

Keywords: Chitosan; Nanoparticle; Respiratory syncytial virus; Viral fusion; Viral replication; shRNA encoding plasmid.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Cytokines / metabolism
Drug Liberation
Female
Inflammation Mediators / metabolism
Intercellular Adhesion Molecule-1 / metabolism
Mice
Mice, Inbred BALB C
Multifunctional Nanoparticles / therapeutic use*
Multifunctional Nanoparticles / ultrastructure
Peptides / pharmacology
Plasmids / genetics
RNA, Small Interfering / metabolism
Respiratory Syncytial Virus Infections / prevention & control*
Respiratory Syncytial Virus Infections / virology
Respiratory Syncytial Virus, Human / drug effects
Respiratory Syncytial Virus, Human / physiology*
Transfection
Viral Fusion Proteins / metabolism

Substances

Cytokines
Inflammation Mediators
Peptides
RNA, Small Interfering
Viral Fusion Proteins
Intercellular Adhesion Molecule-1

Grants and funding

IK6 BX004212/BX/BLRD VA/United States