mproving the eficacy of melanoma treatment remains an important global challenge.Here,we combined chemotherapy with protein tyrosine phosphatase nonreceptor type 2(Ptpn2)based immunotherapy in an effort to address thi...mproving the eficacy of melanoma treatment remains an important global challenge.Here,we combined chemotherapy with protein tyrosine phosphatase nonreceptor type 2(Ptpn2)based immunotherapy in an effort to address this challenge.Shorthairpin RNA(shRNA)targeting Ptpn2 was coencapsulated with doxorubicin(DOX)in the cell membrane of MI macrophages(MIHD@RPR).The prepared nanoparticles(NPs)were effectively phagocytosed by B16F10 cells and MI macrophages,but not by MOmacrophages.Hence,NPevasion from the reticuloendothelial system(RES)was improved and NPenrichment in tumor sites increased.MIHD@RPR can directly kill tumor cells and stimulate immunogenic cell death(ICD)by DOX and downregulate Ptpn2.It can promote Ml macrophage polarization and dendritic cell maturation and increase the proportion of CD8+T cells.MIHD@RPR killed and inhibited the growth of primary melanoma and lung metastatic tumor celis without harming the surrounding tssue.These findings establish MIHD@RPR as a safe multifunctional nanoparticle capable of effectively combining chemotherapy and gene immunotherapies against melanoma.展开更多
基金funded by the National Natural Science Foundation of China(31930067,31800797,31771096,81860543,and 31525009)the National Key Research and Development Program of China(2017YFC1103502)and 1-3-5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYGD18002).
文摘mproving the eficacy of melanoma treatment remains an important global challenge.Here,we combined chemotherapy with protein tyrosine phosphatase nonreceptor type 2(Ptpn2)based immunotherapy in an effort to address this challenge.Shorthairpin RNA(shRNA)targeting Ptpn2 was coencapsulated with doxorubicin(DOX)in the cell membrane of MI macrophages(MIHD@RPR).The prepared nanoparticles(NPs)were effectively phagocytosed by B16F10 cells and MI macrophages,but not by MOmacrophages.Hence,NPevasion from the reticuloendothelial system(RES)was improved and NPenrichment in tumor sites increased.MIHD@RPR can directly kill tumor cells and stimulate immunogenic cell death(ICD)by DOX and downregulate Ptpn2.It can promote Ml macrophage polarization and dendritic cell maturation and increase the proportion of CD8+T cells.MIHD@RPR killed and inhibited the growth of primary melanoma and lung metastatic tumor celis without harming the surrounding tssue.These findings establish MIHD@RPR as a safe multifunctional nanoparticle capable of effectively combining chemotherapy and gene immunotherapies against melanoma.
