- Title
- TLR7 agonist loaded airway epithelial targeting nanoparticles stimulate innate immunity and suppress viral replication in human bronchial epithelial cells
- Creator
- Kan, Stanislav; Grainge, Christopher; Nichol, Kristy; Reid, Andrew; Knight, Darryl; Sun, Yong; Bartlett, Nathan; Liang, Mingtao
- Relation
- International Journal of Pharmaceutics Vol. 617, no. 121586
- Publisher Link
- http://dx.doi.org/10.1016/j.ijpharm.2022.121586
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2022
- Description
- 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-β, 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.
- Subject
- lipid/polymer hybrid nanoparticles; cellular uptake; targeted drug delivery; airway epithelial cells; rhinovirus; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1464492
- Identifier
- uon:47015
- Identifier
- ISSN:0378-5173
- Language
- eng
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