Scheme 1.

“Eat me/don’t eat me” strategy to achieve macrophage escape and improve the tumour targeting efficiency. The cationized mannan-modified extracellular vesicles derived from DC2.4 cells (M-EV) are i.v. injected into the mouse via the tail vein to saturate the receptors of macrophages, prior the administration of a subsequent dose of exosome-hybrid targeted vesicles co-loaded with doxorubicin (DOX) and gefitinib (GE), namely “Hybrid c(RGDm7)-LS-GE/DOX”, thereby minimizing their sequestration by the liver, improving the tumour accumulation and enhancing the therapeutic efficacy on lung cancer.