Extracellular vesicle-like particles from Taraxacum mongolicum suppress non-small cell lung cancer associated with mitochondrial dysfunction

Introduction: Plant-derived extracellular vesicle-like particles (EVLPs) are emerging as natural, orally deliverable nanomaterials, but their antitumor activity and mitochondrial mechanisms in non-small cell lung cancer (NSCLC) remain insufficiently defined. Methods: Taraxacum mongolicum-derived EVLPs (TM-EVLPs) were isolated by enzymatic digestion and differential ultracentrifugation and characterized by nanoparticle tracking analysis, transmission electron microscopy, and protein profiling. Cellular uptake and antitumor effects were evaluated in A549 and H1975 cells using proliferation, migration, invasion, epithelial-mesenchymal transition, and mitochondrial function assays. In vivo efficacy and safety were assessed in an A549 xenograft model after oral TM-EVLP administration. Results: DiI-labeled TM-EVLPs showed clear cell-associated signals after incubation and washing. TM-EVLPs inhibited NSCLC cell viability, DNA synthesis, clonogenicity, migration, and invasion, with more consistent effects at higher concentrations, and increased E-cadherin but decreased N-cadherin expression. TM-EVLP treatment was associated with mitochondrial membrane potential depolarization, increased mitochondrial reactive oxygen species, reduced ATP production, disrupted cristae ultrastructure, and decreased oxidative phosphorylation complex subunits. In xenograft-bearing mice, oral TM-EVLPs (5-20 mg/kg, 15 days) reduced tumor growth, decreased Ki-67 and PCNA staining, increased TUNEL positivity, recapitulated mitochondrial impairment in tumors, and caused no overt histological injury in major organs. Discussion: TM-EVLPs suppress NSCLC malignant phenotypes in association with constrained mitochondrial bioenergetics and increased oxidative stress, supporting a mitochondria-centered stress-linked working model.