Established evidence has unveiled two strategies for treating cancer:depleting tumor-associated macrophages(TAMs)and reprogramming M2-like TAMs into an antitumor M1 phenotype.Here,we designed novel p H-sensitive biomi...Established evidence has unveiled two strategies for treating cancer:depleting tumor-associated macrophages(TAMs)and reprogramming M2-like TAMs into an antitumor M1 phenotype.Here,we designed novel p H-sensitive biomimetic hybrid nanovesicles(EDHPA)loaded with doxorubicin(DOX).DOX@EDHPA can specifically target TAMs by activating macrophage-derived exosomes(M1-Exos)and anisamide(AA)as cancer-specific targeting ligands.In vitro and in vivo studies demonstrated that DOX@EDHPA could efficiently be delivered to the tumor site and taken up by cells.Meanwhile,it synergistically enhanced immunogenic cell death(ICD)and induced a subsequent antigen-specific T cell immune response.The tumor inhibitory rate of the DOX@EDHPA group was 1.42 times that of the free DOX group.Further analysis showed that the excellent antitumor effects of DOX@EDHPA should ascribe to the homing effect of M1-Exos on macrophages and the repolarization to antitumor M1 TAMs,which induced the elevated secretion of pro-infiammatory factors.Therefore,the hybrid EDHPA targeting TAMs to reshape the tumor microenvironment constituted a novel immunochemotherapy strategy to inhibit tumor growth.展开更多
基金supported by the National Natural Science Foundation of China(No.NSFC31872754)。
文摘Established evidence has unveiled two strategies for treating cancer:depleting tumor-associated macrophages(TAMs)and reprogramming M2-like TAMs into an antitumor M1 phenotype.Here,we designed novel p H-sensitive biomimetic hybrid nanovesicles(EDHPA)loaded with doxorubicin(DOX).DOX@EDHPA can specifically target TAMs by activating macrophage-derived exosomes(M1-Exos)and anisamide(AA)as cancer-specific targeting ligands.In vitro and in vivo studies demonstrated that DOX@EDHPA could efficiently be delivered to the tumor site and taken up by cells.Meanwhile,it synergistically enhanced immunogenic cell death(ICD)and induced a subsequent antigen-specific T cell immune response.The tumor inhibitory rate of the DOX@EDHPA group was 1.42 times that of the free DOX group.Further analysis showed that the excellent antitumor effects of DOX@EDHPA should ascribe to the homing effect of M1-Exos on macrophages and the repolarization to antitumor M1 TAMs,which induced the elevated secretion of pro-infiammatory factors.Therefore,the hybrid EDHPA targeting TAMs to reshape the tumor microenvironment constituted a novel immunochemotherapy strategy to inhibit tumor growth.
