TLR7 agonist loaded airway epithelial targeting nanoparticles stimulate innate immunity and suppress viral replication in human bronchial epithelial cells.
Int J Pharm
; 617: 121586, 2022 Apr 05.
Article
en En
| MEDLINE
| ID: mdl-35181464
ABSTRACT
Nanoparticle-based delivery is a strategy for increasing the therapeutic window of inhaled immunomodulatory drugs that have inflammatory activity. TLR7 agonists are a class of immunomodulators that have been considered for the treatment of virus-induced respiratory diseases. However, due to high immune-stimulatory activity, TLR7 agonists, delivered via direct exposure, generally have a narrow therapeutic window. To address this, we have developed lipid/polymer hybrid nanoparticles (NPs) conjugated with anti-EpCAM monoclonal antibody for targeted delivery of TLR7 agonist (CL264) to airway epithelial cells (AECs)2 - the primary site of respiratory virus infection. These airway epithelial targeting nanoparticles (AEC-NPs)3 showed safety and biocompatibility, and approximately two-fold increased cellular uptake compared to non-targeting NPs. Upon cell entry, AEC-NPs were able to deliver CL264 to cytoplasm and endosomes where TLR7 is located. CL264 delivered by AEC-NPs significantly increased innate immune response through expression of IFN-ß, IFN-λ 2/3 and IFN-stimulated genes and suppressed more than 92% of viral load at 48 h post-infection compared to the drug alone and non-targeting NPs. In conclusion, AEC-NPs exhibited increased cellular uptake leading to enhanced innate immune activation and suppression of viral replication. These findings support the use of AEC-targeting approach for delivering drugs with a narrow therapeutic window.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptor Toll-Like 7
/
Nanopartículas
Límite:
Humans
Idioma:
En
Revista:
Int J Pharm
Año:
2022
Tipo del documento:
Article
País de afiliación:
Australia