The immunosuppressive tumor microenvironment(TME)of cancer strongly hinders the anti-tumor immune responses,thereby resulting in disappointing responses to immunotherapy.Chemoattractive and promotive traits of chemoki...The immunosuppressive tumor microenvironment(TME)of cancer strongly hinders the anti-tumor immune responses,thereby resulting in disappointing responses to immunotherapy.Chemoattractive and promotive traits of chemokines exerted on leukocytes have garnered interest in improving the efficiency of immunotherapy by increasing the infiltration of immune cells in the TME.In this study,a folic acid(FA)-modified gene delivery system based on the self-assembly of DOTAP,MPEG-PCL-MPEG,and FA-PEG-PCL-PEG-FA,namely F-PPPD,was developed to deliver plasmids encoding the immunostimulating chemokine CKb11.The delivery of plasmid CKb11(pCKb11)by F-PPPD nanoparticles resulted in the high secretion of CKb11 from tumor cells,which successfully activated T cells,suppressed the M2 polarization of macrophages,promoted the maturation of dendritic cells(DCs),facilitated the infiltration of natural killer(NK)cells and inhibited the infiltration of immunosuppressive cells in tumor tissues.Administration of F-PPPD/pCKb11 also significantly suppressed the cancer progression.Our study demonstrated a nanotechnology-enabled delivery of pCKb11,that remodeled the immunosuppressive TME,for cancer treatment.展开更多
基金the Ministry of Science and Technology of the People’s Republic of China(No.2018ZX09201018)Sichuan Science and Technology Program(No.2019YFS0089,2019YFS0340 and 2020YFS0217)+4 种基金the China Postdoctoral Science Foundation(No.2020M680150)full-time postdoctoral research and development fund of Sichuan University(No.20826041D4048)the full-time postdoctoral research and development fund of West China Hospital of Sichuan University(No.2020HXBH059 and No.2020HXBH002)1·3·5 project of excellent development of discipline of West China Hospital of Sichuan University(No.ZYYC21005)the Natural Science Foundation Youth Project of Jiangsu Province(BK20190989).
文摘The immunosuppressive tumor microenvironment(TME)of cancer strongly hinders the anti-tumor immune responses,thereby resulting in disappointing responses to immunotherapy.Chemoattractive and promotive traits of chemokines exerted on leukocytes have garnered interest in improving the efficiency of immunotherapy by increasing the infiltration of immune cells in the TME.In this study,a folic acid(FA)-modified gene delivery system based on the self-assembly of DOTAP,MPEG-PCL-MPEG,and FA-PEG-PCL-PEG-FA,namely F-PPPD,was developed to deliver plasmids encoding the immunostimulating chemokine CKb11.The delivery of plasmid CKb11(pCKb11)by F-PPPD nanoparticles resulted in the high secretion of CKb11 from tumor cells,which successfully activated T cells,suppressed the M2 polarization of macrophages,promoted the maturation of dendritic cells(DCs),facilitated the infiltration of natural killer(NK)cells and inhibited the infiltration of immunosuppressive cells in tumor tissues.Administration of F-PPPD/pCKb11 also significantly suppressed the cancer progression.Our study demonstrated a nanotechnology-enabled delivery of pCKb11,that remodeled the immunosuppressive TME,for cancer treatment.
