biostudies-literatureUnknownSiddhanta KUniversity of Nebraska Medical CenterNIDDK NIH HHSNCI NIH HHSNIGMS NIH HHSInhalation RNA therapy offers to transform treatment of pulmonary diseases, yet mucus trapping, immune clearance, and navigation of heterogeneous lung tissue architecture still prevents RNA from reaching its target cells. Here, we develop perfluorocarbon (PFC) RNA nanocapsules that show negligible immune clearance, minimal inflammatory response, and efficient mucus transport, while passively homing to lung epithelial and tumor cells. After a single aerosolized dose in orthotopic lung metastasis model, more than 60% of tumor cells and most type II alveolar and bronchial epithelial cells internalized the nanocapsules, with observed pulmonary retention exceeding 48 h. The nanocapsule provoke negligible cytokine release, enabling repeated dosing. Treatment with therapeutic miR34-a suppresses mbioRxiv : the preprint server for biology2025.06.05.658088https://www.ebi.ac.uk/biostudies/studies/S-EPMC12157478biostudies-literatureInhalable Perfluorocarbon RNA Nanocapsules Bypass Immune Clearance While Targeting Lung Epithelial and Lung Tumor Cells.PMC12157478P30 CA036727P20 GM103427R01 DK124095P30 GM127200R01 DK120533P30 GM106397R01 CA235863Oupicky DRavnholdt ARSantarpia JLJogdeo CMDing LKalpana MAWoslager CJSundar ATalmadge JEPoole JAPinkerton BRMonirvaghefi AKumari NSiddhanta KfalseInhalable Perfluorocarbon RNA Nanocapsules Bypass Immune Clearance While Targeting Lung Epithelial and Lung Tumor Cells.Inhalation RNA therapy offers to transform treatment of pulmonary diseases, yet mucus trapping, immune clearance, and navigation of heterogeneous lung tissue architecture still prevents RNA from reaching its target cells. Here, we develop perfluorocarbon (PFC) RNA nanocapsules that show negligible immune clearance, minimal inflammatory response, and efficient mucus transport, while passively homing to lung epithelial and tumor cells. After a single aerosolized dose in orthotopic lung metastasis model, more than 60% of tumor cells and most type II alveolar and bronchial epithelial cells internalized the nanocapsules, with observed pulmonary retention exceeding 48 h. The nanocapsule provoke negligible cytokine release, enabling repeated dosing. Treatment with therapeutic miR34-a suppresses m2025-01-01T00:00:00Z2025 Jun2026-05-01T03:19:17.124Z2026-05-01T03:10:49.67ZS-EPMC121574784050183610.1101/2025.06.05.658088