2026-10-11T04:08:04Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33965959 2026-09-22T15:17:11Z category_696 portal_316 item_type_3 month_year_09_2026

Table 1_Nebulized Polygonum cuspidatum-derived nanovesicles loaded with dexamethasone synergistically ameliorate acute lung injury via metabolic-immune reprogramming.docx Zibin Jiang (2255836) Fan Shen (47072) Fang Cheng (138729) Jianwei Dai (11011722) Dongxing Zhao (545522) Genetic Immunology acute lung injury (ALI) dexamethasone macrophage polarization nebulized inhalation Polygonum cuspidatum-Derived Nanovesicles (PcDNs) Background<p>Systemic glucocorticoid therapy for acute lung injury (ALI) is frequently limited by poor pulmonary targeting and severe systemic side effects. To address these challenges, we developed a bio-inspired, inhalable nanoplatform using naturally derived nanovesicles from the medicinal plant Polygonum cuspidatum (PcDNs) to actively deliver dexamethasone (PcDNs@Dex) via nebulization.</p>Methods<p>We assessed the post-nebulization stability of the nanosystem and evaluated its therapeutic efficacy in vitro and in vivo. In vitro, we investigated macrophage polarization (M1/M2) and the associated signaling pathways. Untargeted metabolomics was employed to analyze metabolic reprogramming. In vivo, a murine lipopolysaccharide (LPS)-induced ALI model was utilized to assess pulmonary targeting, alveolar damage, vascular permeability, and cytokine production.</p>Results<p>Unlike conventional inert synthetic carriers, PcDNs function as intrinsic synergistic therapeutics. PcDNs@Dex maintained robust structural and functional stability post-nebulization, ensuring efficient targeted pulmonary delivery. In vitro, PcDNs@Dex exerted superior anti-inflammatory and cytoprotective effects by actively reprogramming macrophages from a pro-inflammatory M1 to a pro-resolving M2 phenotype, synergistically mediated through the coordinated inhibition of NF-κB and JAK-STAT signaling pathways. Crucially, untargeted metabolomics unveiled a novel immunometabolic mechanism: PcDNs inherently act as bioactive modulators that restore glycerophospholipid metabolic homeostasis, thereby stabilizing cell membranes and restricting pro-inflammatory mediator production at the metabolic level. In an LPS-induced ALI model, nebulized PcDNs@Dex precisely targeted the pulmonary niche, significantly attenuating alveolar damage, reducing vascular permeability, and suppressing the local cytokine storm.</p>Conclusion<p>This dual intervention effectively promoted a reparative immune microenvironment while exhibiting excellent systemic safety. These results establish PcDNs@Dex as a promising, multi-target strategy that integrates targeted delivery with synergistic bioactivity for managing inflammatory lung diseases.</p> 2026-09-22T15:17:11Z Dataset Dataset 10.3389/fimmu.2026.1872209.s001 https://figshare.com/articles/dataset/Table_1_Nebulized_Polygonum_cuspidatum-derived_nanovesicles_loaded_with_dexamethasone_synergistically_ameliorate_acute_lung_injury_via_metabolic-immune_reprogramming_docx/33965959 CC BY 4.0