.png){kind=icon}
.png){kind=icon}
Return
Acacetin-incorporated lipid nanoparticles for inhaled mRNA vaccines
.png){kind=icon}
PRE
AI
X
K
Y
Y
Y
X
Z
Q
Y
N
S
J
Z
DOI：10.1039/D5NH00794A.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Inhaled mRNA vaccines have shown great promise for the prevention of respiratory diseases. However; their broad application is still restricted by lipid nanoparticle (LNP)-induced oxidative stress; rapid clearance of LNPs from the lung; and limited mRNA expression. Here; we show that incorporating a natural compound; acacetin; into the LNP formulation can overcome these delivery barriers and greatly improve inhaled vaccine effectiveness. A natural compound library containing 242 compounds was used in an in vitro screening experiment; and acacetin was identified as the lead compound that substantially increased LNP-mediated mRNA expression in A549 cells. We then incorporated acacetin in LNPs as a fifth component. After optimizing the formulation of LNPs in in vitro transfection assays and in vivo pulmonary delivery assays; we find acacetin-incorporated LNPs increased lung transfection by 10.82-fold. A mechanistic study showed that acacetin reshaped the intracellular environment of lung cells by activating antioxidant stress pathways and suppressing pro-inflammatory signaling; thereby maintaining high levels of mRNA translation. Inhaled administration of acacetin-incorporated LNPs; delivering mRNA encoding the SARS-CoV-2 spike protein; induced higher antigen-specific IgG (14.95-fold) and IgA (2.38-fold) levels than a conventional LNP formulation; without inducing toxicity. We demonstrate that acacetin-incorporated LNPs offer a simple and scalable strategy to improve the efficacy of inhaled mRNA vaccines.
Journal
N
IF:
0
Papers:
99
Citations:
0
Organization
Cited Papers