Construction of <scp>PEI‐EGFR‐PD‐L1‐siRNA</scp> dual functional nano‐vaccine and therapeutic efficacy evaluation for lung cancer
Guixue Yang, Dong Zhou, Yin Dai, Yanqi Li, Jiang Wu, Quanxing Liu, Xu‐Feng Deng
Abstract
BACKGROUND: PD-1/PD-L1 tumor immunotherapy shows effective anticancer in treatment of solid tumors, so PEI lipid nanoparticles (PEI-LNP)/siRNA complex (EPV-PEI-LNP-SiRNA) with the therapeutic function of PD-L1-siRNA and EGFR short peptide/PD-L1 double immune-enhancing function were constructed for the prevention and treatment of EGFR-positive lung cancer in this study. METHOD: In this study, PEI lipid nanoparticles (PEI-LNP)/siRNA complex (EPV-PEI-LNP-siRNA) with the therapeutic function of PD-L1-siRNA and EGFR short peptide/PD-L1 double immune-enhancing function were constructed for the prevention and treatment of EGFR-positive lung cancer and functional evaluation was conducted. RESULTS: On the basis of the construction of the composite nano-drug delivery system, the binding capacity, cytotoxicity, apoptosis and uptake capacity of siRNA and EPV-PEI-LNP were tested in vitro, and the downregulation effect of PD-L1 on A549 cancer cells and the cytokine levels of cocultured T cells were tested. Lipid nanoparticles delivered siRNA and EGFR short peptide vaccine to non-small cell lung cancer (NSCLC), increasing tumor invasion and activation of CD8 + T cells. Combination therapy is superior to single target therapy. CONCLUSION: Our constructed lipid nanoparticles of tumor targeted therapy gene siRNA combination had the ability to target cells in vitro and downregulate the expression of PD-L1, realizing the tumor-specific expression of immune-stimulating cytokines, which is a highly efficient and safe targeted therapy nano-vaccine.