Beyond traditional endothelium-dependent vessel(EDV),vascular mimicry(VM)is another critical tumor angiogenesis that further forms in many malignant metastatic tumors.However,the existing anti-angiogenesis combined ch...Beyond traditional endothelium-dependent vessel(EDV),vascular mimicry(VM)is another critical tumor angiogenesis that further forms in many malignant metastatic tumors.However,the existing anti-angiogenesis combined chemotherapeutics strategies are only efficient for the treatment of EDV-based subcutaneous tumors,but remain a great challenge for the treatment of in situ malignant metastatic tumor associated with EDV and VM.Here,we demonstrate a self-assembled nanoparticle(VE-DDP-Pro)featuring self-anti-EDV and-VM capacity enables to significantly enhance the treatment efficacy of cisplatin(DDP)against the growth and metastasis of ovarian cancer.The VE-DDP-Pro is constructed by patching DDP loaded cRGD-folate-heparin nanoparticles(VE)onto the surface of protamine(Pro)nanoparticle.We demonstrated the self-anti-angiogenesis capacity of VE-DDP-Pro was attributed to VE,which could significantly inhibit the formation of EDV and VM by regulating signaling pathway of MMP-2/VEGF,AKT/mTOR/MMP-2/Laminin and AKT/mTOR/EMT,facilitating chemotherapeutics to effectively suppress the development and metastasis of ovarian cancer.Thus,combing with the chemotherapeutics effectiveness of DDP,the VE-DDP-Pro can significantly enhance treatment efficacy and prolong median survival of mice with metastatic ovarian cancer.We believe our self-assembled nanoparticles integrating the anti-EDV and anti-VM capacity provide a new preclinical sight to enhance the efficacy of chemotherapeutics for the treatment malignant metastasis tumor.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(No.22075127,81773291,21872158)Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110105005)atural Science Foundation of Guangdong Province(2021A1515011638).
文摘Beyond traditional endothelium-dependent vessel(EDV),vascular mimicry(VM)is another critical tumor angiogenesis that further forms in many malignant metastatic tumors.However,the existing anti-angiogenesis combined chemotherapeutics strategies are only efficient for the treatment of EDV-based subcutaneous tumors,but remain a great challenge for the treatment of in situ malignant metastatic tumor associated with EDV and VM.Here,we demonstrate a self-assembled nanoparticle(VE-DDP-Pro)featuring self-anti-EDV and-VM capacity enables to significantly enhance the treatment efficacy of cisplatin(DDP)against the growth and metastasis of ovarian cancer.The VE-DDP-Pro is constructed by patching DDP loaded cRGD-folate-heparin nanoparticles(VE)onto the surface of protamine(Pro)nanoparticle.We demonstrated the self-anti-angiogenesis capacity of VE-DDP-Pro was attributed to VE,which could significantly inhibit the formation of EDV and VM by regulating signaling pathway of MMP-2/VEGF,AKT/mTOR/MMP-2/Laminin and AKT/mTOR/EMT,facilitating chemotherapeutics to effectively suppress the development and metastasis of ovarian cancer.Thus,combing with the chemotherapeutics effectiveness of DDP,the VE-DDP-Pro can significantly enhance treatment efficacy and prolong median survival of mice with metastatic ovarian cancer.We believe our self-assembled nanoparticles integrating the anti-EDV and anti-VM capacity provide a new preclinical sight to enhance the efficacy of chemotherapeutics for the treatment malignant metastasis tumor.
