Dual-targeting nanovesicles enhance specificity to dynamic tumor cells in vitro and in vivo via manipulation of αvβ3-ligand binding

The dynamic or flowing tumor cells just as leukemia cells and circulating tumor cells face a microenvironment difference from the solid tumors,and the related targeting nanomedicines are rarely reported.The existence of fluidic shear stress in blood circulation seems not favorable for the binding of ligand modified nanodrugs with their target receptor.Namely,the binding feature is very essential in this case.Herein,we utilized HSPC,PEG-DSPE,cholesterol and two avb3 ligands(RGDm7 and DT4)with different binding rates to build dual-targeting nanovesicles,in an effort to achieve a"fast-binding/slow-unbinding"function.It was demonstrated that the dual-targeting nanovesicles actualized effi-cient cellular uptake and antitumor effect in vitro both for static and dynamic tumor cells.Besides,the potency of the dual-targeting vesicles for flowing tumor cells was better than that for static tumor cells.Then,a tumor metastasis mice model and a leukemia mice model were established to detect the killing ability of the drug-loaded dual-targeting vesicles to dynamic tumor cells in vivo.The therapy efficacy of the dual-targeting system was higher than other controls including single-targeting ones.Generally,it seems possible to strengthen drug-targeting to dynamic tumor cells via the control of ligandereceptor interaction.