Comparative effects of extracellular vesicles and liposomal nanocarriers on bleomycin-induced stress in A549 human adenocarcinoma cells

Lung cancer and chronic respiratory diseases are among the leading causes of death worldwide. Key factors in their pathogenesis include reactive oxygen species (ROS), transforming growth factor-β1 (TGF-β1) and epithelial-mesenchymal transition (EMT). Exogenous antioxidants can mitigate the oxidative stress that drives TGF-β1-mediated respiratory pathologies. Given their role in cellular communication and natural biocompatibility, extracellular vesicles (EVs) are emerging as promising candidates for the delivery of therapeutic cargo to pathological cells. Notably, microalgal-derived EVs (i.e., nanoalgosomes) have been shown to exhibit antioxidant and anti-inflammatory activity. In this study, the bioactivity of EVs derived from Tetraselmis chuii (CCAP 66/21B) was investigated in a bleomycin-stressed (8 µg mL^-1) human adenocarcinoma alveolar epithelial cell model (A549). Moreover, the effects of these EVs were compared to liposomes loaded with established therapeutics (pirfenidone and quercetin), synthesised using the lipid film hydration method. In vitro assessments included cell viability (MTS), intracellular ROS, morphological changes, cell migration, EMT-related mRNA expression (qPCR), and TGF-β1 release (ELISA). Both the EVs (nanoalgosomes) and pirfenidone- and quercetin-loaded liposomal nanocarriers (1-4 µg mL^-1) effectively attenuated bleomycin-induced EMT, inhibited cell migration, suppressed profibrotic TGF-β1, lowered intracellular ROS and upregulated glutathione peroxidase 4 (GPX4). Importantly, the innate bioactive cargo of the naturally derived nanoalgosomes exhibited comparable effects to the liposome therapeutic formulations in mitigating bleomycin-induced stress in A549 cells.