In vivo evaluation of EGFRapt-3WJ-siKRASG12C pRNA nanoparticles on NSCLC tumor xenograft models
(A) IVIS lumina imaging system was used to study the biodistribution of Alexa 750-labeled EGFRapt-3WJ-siKRASG12C pRNA nanoparticles in live mice (top panels) and dissected organs ex vivo (bottom panels). (B) Dosing schematic of pRNA nanoparticle injection and tumor isolation for dose optimization study. (C and D) After four intravenous administrations of increasing doses of EGFRapt-3WJ-siKRASG12C pRNA nanoparticles, KRAS mRNA expression (C) in tumor xenografts was quantified by qRT-PCR, and activation status of KRAS downstream MAPK pathway signaling was evaluated by p-ERK immunoblotting (D). (E and F) Tumor growth curve of H2122 and H2030 xenograft mouse models, which were treated with pRNA nanoparticles two times a week for 3 weeks (n = 10 mice per group). Error bars represent SEM. Significance was calculated using one-way ANOVA analysis followed by Tukey’s post-hoc test: ∗∗p < 0.001.