Fig. 5: Inhaled CAS-LNP delivers mRNA to specific cells of mice.

Three-dimensional fluorescent imaging of lungs in mice treated with inhaled SM102-LNP (a) or CAS-LNP (b) encapsulating Cy5-mEGFP at 30 min post-administration. Green and red signals represent EGFP and Cy5, respectively. Representative confocal microscopy images of excised tracheas (c) and lungs (e). Quantitative analysis of Cy5 fluorescence intensity in trachea (d) (n = 8 technical replicates) and pulmonary parenchyma (f) (n = 10 technical replicates). Data are shown as mean ± SD. Statistical significance was analyzed by unpaired two-tailed Student’s t test. g Treatment scheme for evaluating the mRNA expression in different cell types of inhaled CAS-LNP or intravenously injected IV-LNP. Each mouse received 5 µg of mCre per dose. h Schematic illustrating that the expression of Cre recombinase deletes the stop cassette and activates the expression of tdTomato in C57BL/6-Rosa26-CAG-LSL-tdTomato mice. i Representative flow cytometry measurements and quantitative analysis (j) of immune cells (CD45), endothelial cells (CD31), and epithelial cells (CD326) expressing tdTomato in the lungs after different treatments (n = 3 biologically independent samples). Data are shown as mean ± SEM. k The percentage of tdTomato + dendritic cell, alveolar macrophage, interstitial macrophage, neutrophil, B cell, T cell, and NK cell among immune cells of CAS-LNP treated lungs (n = 4 biologically independent samples). Figure 5c and e were created in BioRender. Lu, X. (2024) BioRender.com/m16g625. Figure 5g was created in BioRender. Lu, X. (2024) BioRender.com/j51w648. Figure 5h was created in BioRender. Lu, X. (2024) BioRender.com/m96i222. Source data are provided as a Source Data file.