Recombinant PD1 liposome loading nintedanib for pulmonary fibrosis therapy in mice

Pulmonary fibrosis is a traumatic lung disease characterized by excessive proliferation of lung fibroblasts and excessive deposition of extracellular matrix. There is clinical need for the development of efficient drug delivery system to treat this severe disorder. Here, we report a recombinant PD1 liposome loaded with nintedanib (rLipo nidanib) for pulmonary fibrosis therapy. The functional verification shows that it can target the lung fibroblast, inhibit the proliferation of lung fibroblast, reduce dense fibrosis areas and collagen deposition, and extend the survival period of the pulmonary fibrosis-bearing mice. The mechanism study reveals that it reduces the phosphorylated growth factor receptors and expression of PD-L1 in lung fibroblast, and blocks the binding between PD1 on immune cell and PD-L1 on lung fibroblast. The study hints a new approach for enhancing therapy efficacy of pulmonary fibrosis by targeted drug delivery along with immunoblockade strategy. Summary: Recombinant PD1 liposome loaded with nintedanib provides a new approach for enhancing therapy efficacy of pulmonary fibrosis in mice by targeted drug delivery along with immunoblockade strategy. • PD1 liposome loading nintedanib inhibits collagen deposition of pulmonary fibrosis. • It acts PD1/PD-L1 immunoblockade role between immune cell and lung fibroblast. • It exhibits remarkable efficacy in prolonging mice survival period.