A multifunctional nanotheranostic agent potentiates erlotinib to EGFR wild-type non-small cell lung cancer

Epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKI),such as Erlotinib,have demonstrated remarkable efficacy in the treatment of non-small cell lung cancer(NSCLC)patients with mutated EGFR.However,the efficacy of EGFR-TKIs in wild-type(wt)EGFR tumours has been shown to be marginal.Methods that can sensitize Erlotinib to EGFR wild-type NSCLC remain rare.Herein,we developed a multifunctional superparamagnetic nanotheranostic agent as a novel strategy to potentiate Erlotinib to EGFR-wt NSCLCs.Our results demonstrate that the nanoparticles can co-escort Erlotinib and a vascular epithermal growth factor(VEGF)inhibitor,Bevacizumab(Bev),to EGFR-wt tumours.The nanotheranostic agent exhibits remarkable effects as an inhibitor of EGFR-wt tumour growth.Moreover,Bev normalizes the tumour embedded vessels,further promoting the therapeutic efficacy of Erlotinib.In addition,the tumour engagement of the nanoparticles and the vascular normalization could be tracked by magnetic resonance imaging(MRI).Collectively,our study,for the first time,demonstrated that elaborated nanoparticles could be employed as a robust tool to potentiate Erlotinib to EGFR-wt NSCLC,paving the way for imaging-guided nanotheranostics for refractory NSCLCs expressing EGFR wild-type genes.