Fluorescent Pirfenidone-Cerium(III) nanocomplexes protect against radiation-induced pulmonary fibrosis and inhibit tumor cell growth

Radiation-induced pulmonary fibrosis (RIPF) is a common adverse effect of thoracic radiation therapy. Although pirfenidone is approved for treating pulmonary fibrosis, its utility is limited by its short half-life and ability to scavenge reactive oxygen species (ROS). Thus, a nanoscale complexes of cerium(III), 10-carboxyl-pirfenidone, and 1,10-phenanthroline (NPs Ce(phen)Pirf 3 ) was developed to prevent RIPF in a mouse model. NPs Ce(phen)Pirf 3 was successfully prepared using a simple moderate solvothermal method and characterized using FTIR , electrospray ionization MS , 1H nuclear magnetic NMR, and transmission electron microscopy . The cerium(III) nanocomplexes exhibited a near-spherical shape and dissolved in water with a diameter of ∼125.2  nm , as characterized by dynamic light scattering . Compared with pirfenidone, NPs Ce(phen)Pirf 3 with blue fluorescence exhibited prolonged retention times with thoracic-specific accumulation in vivo. Mice received 15 Gy gamma-ray treatment on the thorax with or without NPs Ce(phen)Pirf 3 or pirfenidone administration. NPs Ce(phen)Pirf 3 improved lung function, alleviated radiation-induced pathological changes in the lung tissues, and reduced collagen deposition 16 weeks after radiation. Our results from in vivo and in vitro experiments demonstrated that NPs Ce(phen)Pirf 3 increased the ROS-scavenging ability. Additionally, NPs Ce(phen)Pirf 3 regulated epithelial-mesenchymal transition (EMT)-related proteins, including up-regulate E-cadherin and down-regulate N-cadherin, α-SMA, and TGF-β1 in RLE-6TN cells, which suggested NPs Ce(phen)Pirf 3 may alleviate RIPF by inhibiting EMT. Finally, NPs Ce(phen)Pirf 3 also inhibited the growth of thoracic tumor cells in mice. NPs Ce(phen)Pirf 3 had a protective role against RIPF and antitumor effects, suggesting that they are a promising therapy for thoracic radiation-induced RIPF.