Fig. 8: The cLMNB1-mut encapsulated in LNPs is promising to overcome osimertinib resistance.

A, B PC9OR and HCC827OR cells were stably transfected with DOX-ON-cLMNB1, DOX-ON-cLMNB1-mut, or the corresponding empty vectors. Mice bearing PC9OR and HCC827OR cell xenograft tumors were treated with Osi for 20 days (n = 5). C Schematic diagram of cLMNB1-mut (left). The junction sequence was verified by Sanger sequencing (right). D Bioluminescence imaging assay of mice at 8 h and 24 h after injection of F-luc-LNP through the tail vein. E Mouse lungs were orthotopically transplanted with PC9OR-luci cells, and then mice were given PBS, Osi, LNP, Osi + LNP, followed by treatment cessation and follow-up (n = 5). F Bioluminescence imaging of nude mice every 10 days. G Kaplan–Meier survival analysis of nude mice. H Hematoxylin-eosin (H&E, 40×) and Immunohistochemistry (FGFR4, Ki-67, and TUNEL stain, 40×) analysis of mouse lungs. Scale bar, 50 μm. I–K IHC score of FGFR4, per cent Ki-67 positive cells, and per cent area necrosis were plotted. L Western blot for protein levels of FGFR4 in the mouse tumors treated with PBS and LNP (n = 5). M H&E (40×) and Immunohistochemistry (FGFR4 stain, 40×) analysis of sensitive and resistant patient lungs. Scale bar, 50 μm. N Pearson’s correlation between FGFR4 protein and cLMNB1 RNA expression in our osimertinib resistance LUAD sample cohort (n = 20). Three independent experiments were conducted for each result. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 compared with the controls.