Objective The aims of this study were to develop targeted cationic microbubbles conjugated with a CD 105 antibody (CMB 105) for use in targeted vascular endothelial cell gene therapy and ultrasound imaging, and then compared the results with untargeted cationic microbubbles (CMB) and neutral microbubbles (NMB).Methods CMB105 were prepared and compared with untargeted CMB and NMB.First,the microbubbles were characterized in terms of size, zeta-potential, antibody binding ability and plasmid DNA loading capacity.A tumor model of subcutaneous breast cancer in nude mice was used for our experiments.The ability of different types of microbubbles to target HUVECs in vitro and tumor neovascularization in vivo was measured.The endostatin gene was selected for its outstanding antiangiogenesis effect.In vitro experiments,the transfection efficiency and cell cycle were analyzed using flow cytometry, the transcription and expression of endostatin were measured by qPCR and Western Blot, respectively.Experiments on vascular tube cavity formation and tumor cells invasion were used to evaluate the antiangiogenesis gene therapy efficiency in vitro.Tumors were exposed to ultrasound irradiation with different types of microbubbles,the gene therapy effects were investigated through detecting the apoptosis induction and change of tumor volume.Results CMB105 and CMB differed significantly from NMB in terms of zeta-potential,the DNA loading capacities were (16.76± 1.75) μg, (18.21 ± 1.22) μg, and (0.48±0.04) μg per 5 × 108 microbubbles, respectively.The charge-coupling of plasmid DNA to CMB 105 was not affected by the presence of the CD105 antibody.Both CMB 105 and CMB could target to HUVECs in vitro,while only C MB105 could target to tumor neovascularization in vivo.In vitro experiments,the transfection efficiency of CMB105 was 24.7-fold higher than the transfection efficiency of NMB and 1.47-fold higher than the transfection efficiency of CMB (P<0.05).By ultrasound-targeted microbubble destruction (UTMD)-mediated gene therapy,the transcription and expression of endostatin were the highest in the CMB105 group (P<0.001);the antiangiogenesis effect and inhibition of tumor cells invasion was better with C MB 105 than CMB or NMB in vitro(P<0.01).After gene therapy, the tumor volumes of CMB 105 group were significantly smaller than that of CMB and NMB group, and lots of tumor cells had begun apoptosis in the C MB 105 group,the apoptosis index was highest in the CMB 105 group(P<0.001).Conclusion As a contrast agent and plasmid carrier, CMB105 can be used not only for targeted ultrasound imaging but also for targeted gene therapy both in vitro and in vivo.The plasmid DNA binding ability of the CMB was not affected by conjugation of the CMB with the CD105 antibody,and because of its targeting ability,the gene transfection efficiency and therapeutic effect were better compared to the untargeted CMB and NMB.The advantages of targeted gene therapy with CMB105 in vivo were more prominent than with CMB or NMB because both of the latter cannot target to the endothelia in vivo.