Liposomes actively recognizing the glucose transporter GLUT1 and integrin αvβ3 for dual‐targeting of glioma

Abstract The treatment of glioma is a great challenge because of the existence of the blood–brain barrier (BBB). In order to develop an efficient glioma‐targeting drug delivery system to greatly improve the brain permeability of anti‐cancer drugs and target glioma, a novel glioma‐targeted glucose‐RGD (Glu‐RGD) derivative was designed and synthesized as ligand for preparing liposomes to effectively deliver paclitaxel (PTX) to cross the BBB and target glioma. The liposomes were prepared and characterized for particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis, and cell cytotoxicity. Also, the Glu‐RGD modified liposomes showed superior targeting ability in in vitro and in vivo evaluation as compared to naked PTX, non‐coated, singly modified liposomes and liposomes co‐modified by physical blending. The relative uptake efficiency and concentration efficiency were enhanced by 4.41‐ and 4.72‐fold compared to that of naked PTX, respectively. What is more, the Glu‐RGD modified liposomes also displayed the maximum accumulation of DiD‐loaded liposomes at tumor sites compared to the other groups in in vivo imaging. All the results in vitro and in vivo suggested that Glu‐RGD‐Lip would be a potential delivery system for PTX to treat integrin αvβ3‐overexpressing tumor‐bearing mice.