Tumor associated macrophages(TAMs)tend to exhibit tumor-promoting M2 phenotype and contribute to the development of immunosuppressive microenvironment of solid tumors.Reprograming TAMs from M2 into tumoricidal M1 phen...Tumor associated macrophages(TAMs)tend to exhibit tumor-promoting M2 phenotype and contribute to the development of immunosuppressive microenvironment of solid tumors.Reprograming TAMs from M2 into tumoricidal M1 phenotype is robust for stimulating tumor immunosuppressive microenvironment(TIME).In this study,we developed a poly(amidoamine)(PAMAM)derivative dendrimer(denoted as fourth generation-N,N-diethylaminoethyl(G4-DEEA))for efficient loading of Toll-like receptor 7 and 8(TLR7/8)agonist(R848)to remodel the TIME for potent cancer immunotherapy,G4-DEEA exhibited a high loading capacity of R848 up to 35.9 wt%by taking advantage of its dendritic structure.The resulting formulation(designated as G4-DEEA@R848)effectively polarized M2 macrophages into M1 phenotype in vitro,and improved the maturation and activation of antigen-presenting cells.In the 4T1 orthotopic breast cancer model,G4-DEEA@R848 showed a stronger tumor inhibitory effect than free drug.The mechanistic studies suggested that G4-DEEA@R848 could significantly stimulate the TIME by repolarizing TAMs into M1 phenotype,reducing the presence of immunosuppressive myeloid cells and increasing the infiltration of tumor cytotoxic T cells.This study provides a simple but effective dendrimer-based strategy to improve the formulation of R848 for improved cancer immunotherapy.展开更多
In order to control the size and shape of Ag nanoparticles obtained by using poly（amidoamine） （PA- MAM） dendrimer as template, the complexation between Ag^＋ ions and dendrimer studied extensively by UV-Vis spectr...In order to control the size and shape of Ag nanoparticles obtained by using poly（amidoamine） （PA- MAM） dendrimer as template, the complexation between Ag^＋ ions and dendrimer studied extensively by UV-Vis spectroscopy and FTIR. After the Ag＋/PAMAM demdrimer being reduced by direct chemical reduction, Ag （0） nanopartides was formed, whose structure and characterization were studied by UV-Vis spectroscopy, transmission electron microscopy （TEM） and electron diffraction （ED） respectively. The results reveal that Ag nanopartides is a kind of face center cubic crystal and its average size is 4.5 nm. The solubility and stability of the solution containing Ag nanopartides also indicate that dendrimer is a good kind of template, as well as a protective agent.展开更多
基金supported by National Key R&D Program of China(No.2017YFA0205600)Guangdong Natural Science Funds for Distinguished Young Scholar(No.2017A030306018)+2 种基金National Natural Science Foundation of China(Nos.51922043 and 31771091)Guangdong Provincial Programs(Nos.2017ZT07S054 and 2017GC010304)the Science and Technology Program of Guangzhou(No.201902020018),and Fundamental Research Funds for Central Universities.
文摘Tumor associated macrophages(TAMs)tend to exhibit tumor-promoting M2 phenotype and contribute to the development of immunosuppressive microenvironment of solid tumors.Reprograming TAMs from M2 into tumoricidal M1 phenotype is robust for stimulating tumor immunosuppressive microenvironment(TIME).In this study,we developed a poly(amidoamine)(PAMAM)derivative dendrimer(denoted as fourth generation-N,N-diethylaminoethyl(G4-DEEA))for efficient loading of Toll-like receptor 7 and 8(TLR7/8)agonist(R848)to remodel the TIME for potent cancer immunotherapy,G4-DEEA exhibited a high loading capacity of R848 up to 35.9 wt%by taking advantage of its dendritic structure.The resulting formulation(designated as G4-DEEA@R848)effectively polarized M2 macrophages into M1 phenotype in vitro,and improved the maturation and activation of antigen-presenting cells.In the 4T1 orthotopic breast cancer model,G4-DEEA@R848 showed a stronger tumor inhibitory effect than free drug.The mechanistic studies suggested that G4-DEEA@R848 could significantly stimulate the TIME by repolarizing TAMs into M1 phenotype,reducing the presence of immunosuppressive myeloid cells and increasing the infiltration of tumor cytotoxic T cells.This study provides a simple but effective dendrimer-based strategy to improve the formulation of R848 for improved cancer immunotherapy.
文摘In order to control the size and shape of Ag nanoparticles obtained by using poly（amidoamine） （PA- MAM） dendrimer as template, the complexation between Ag^＋ ions and dendrimer studied extensively by UV-Vis spectroscopy and FTIR. After the Ag＋/PAMAM demdrimer being reduced by direct chemical reduction, Ag （0） nanopartides was formed, whose structure and characterization were studied by UV-Vis spectroscopy, transmission electron microscopy （TEM） and electron diffraction （ED） respectively. The results reveal that Ag nanopartides is a kind of face center cubic crystal and its average size is 4.5 nm. The solubility and stability of the solution containing Ag nanopartides also indicate that dendrimer is a good kind of template, as well as a protective agent.
