The interplay among diverse cell populations in the tumor microenvironment contributes to tumor progression.Targeting to different cell populations might result in improved therapeutic effects on malignant tumors.Inte...The interplay among diverse cell populations in the tumor microenvironment contributes to tumor progression.Targeting to different cell populations might result in improved therapeutic effects on malignant tumors.Integrins high express on many kinds of tumor cells,and VEGF has a strong effect on tumor angiogenesis.Therefore,based on tumor cells and angiogenesis,we fabricated integrin-targeting cRGD-DOX nanoparticles and combined them with the anti-VEGF antibody bevacizumab.We evaluated the antitumor effect of this combination therapy in an integrin-overexpressing MDA-MB-231 tumor model.The cRGD-DOX nanoparticles were effectively uptake by MDA-MB-231 cells and the uptake was related to the expression of integrinin;cRGD-DOX nanoparticles showed less cytotoxic than free DOX;Bevacizumab did not show significant cytotoxicity against MDA-MB-231 cells at concentrations less than 1 mg/mL.The in vivo results showed that bevacizumab could reduce tumor interstitial fluid pressure;the combination of bevacizumab and cRGD-DOX nanoparticles showed enhanced antitumor effects compared with the corresponding single-agent treatments.These findings suggested the combination of angiogenesis antibody and integrin-targeting nanoparticle loaded with a cytotoxic drug was a promising cancer treatment regimen.展开更多
基金National Natural Science Foundation of China(Grant No.81690264)the National Key Research and Development Program of China(Grant No.2017YFA0205600)Beijing Natural Science Foundation(Grant No.7162108)
文摘The interplay among diverse cell populations in the tumor microenvironment contributes to tumor progression.Targeting to different cell populations might result in improved therapeutic effects on malignant tumors.Integrins high express on many kinds of tumor cells,and VEGF has a strong effect on tumor angiogenesis.Therefore,based on tumor cells and angiogenesis,we fabricated integrin-targeting cRGD-DOX nanoparticles and combined them with the anti-VEGF antibody bevacizumab.We evaluated the antitumor effect of this combination therapy in an integrin-overexpressing MDA-MB-231 tumor model.The cRGD-DOX nanoparticles were effectively uptake by MDA-MB-231 cells and the uptake was related to the expression of integrinin;cRGD-DOX nanoparticles showed less cytotoxic than free DOX;Bevacizumab did not show significant cytotoxicity against MDA-MB-231 cells at concentrations less than 1 mg/mL.The in vivo results showed that bevacizumab could reduce tumor interstitial fluid pressure;the combination of bevacizumab and cRGD-DOX nanoparticles showed enhanced antitumor effects compared with the corresponding single-agent treatments.These findings suggested the combination of angiogenesis antibody and integrin-targeting nanoparticle loaded with a cytotoxic drug was a promising cancer treatment regimen.
