The cytomembrane-derived delivery platform represents a promising biomimetic strategy in oncotherapy.To achieve durable and reliable tumor inhibition,mature dendrosomes(mDs),which were isolated from bone marrow-derive...The cytomembrane-derived delivery platform represents a promising biomimetic strategy in oncotherapy.To achieve durable and reliable tumor inhibition,mature dendrosomes(mDs),which were isolated from bone marrow-derived dendritic cells undergoing CT26 tumor antigen(TA)stimulation,were fused with redox-responsive nanoparticles(NPs)that were composed of poly(disulfide ester amide)polymers with an intensified disulfide density and hydrophobic oxaliplatin(OXA)prodrugs with the ability to potentiate immunogenicity.In vitro and in vivo results revealed that NP/mDs could induce tumor cell death through mitochondrial pathway and thus created immunogenic microenvironments,but also elicited immunocyte differentiation by TA cross-dressing and infiltration by direct presentation.By further neutralizing immune-regulatory interaction,the administration of PD-L1 antibody(αPD-L1)greatly improved antitumor efficiency of NP/mDs.Furthermore,the effectors of host immune systems effectively inhibited the growth and metastasis of distal tumors,likely because the autologous TA evoked by OXA and allogeneic TA delivered by mDs acted as additional stimuli to reinforce the immune response of tumor-specific T cells and immunosurveillance toward oncogenesis.These results demonstrated that NP/mDs could simultaneously realize immunogenic chemotherapeutics and specific TA delivery.In combination withαPD-L1,the antitumor effect was further enhanced.Therefore,NP/mDs provide a promising strategy for the comprehensive treatment of malignancy.展开更多
基金supported by the National Natural Science Foundation of China(No.81773911,81690263 and 81573616)the Development Project of Shanghai Peak Disciplines-Integrated Medicine(No.20180101).
文摘The cytomembrane-derived delivery platform represents a promising biomimetic strategy in oncotherapy.To achieve durable and reliable tumor inhibition,mature dendrosomes(mDs),which were isolated from bone marrow-derived dendritic cells undergoing CT26 tumor antigen(TA)stimulation,were fused with redox-responsive nanoparticles(NPs)that were composed of poly(disulfide ester amide)polymers with an intensified disulfide density and hydrophobic oxaliplatin(OXA)prodrugs with the ability to potentiate immunogenicity.In vitro and in vivo results revealed that NP/mDs could induce tumor cell death through mitochondrial pathway and thus created immunogenic microenvironments,but also elicited immunocyte differentiation by TA cross-dressing and infiltration by direct presentation.By further neutralizing immune-regulatory interaction,the administration of PD-L1 antibody(αPD-L1)greatly improved antitumor efficiency of NP/mDs.Furthermore,the effectors of host immune systems effectively inhibited the growth and metastasis of distal tumors,likely because the autologous TA evoked by OXA and allogeneic TA delivered by mDs acted as additional stimuli to reinforce the immune response of tumor-specific T cells and immunosurveillance toward oncogenesis.These results demonstrated that NP/mDs could simultaneously realize immunogenic chemotherapeutics and specific TA delivery.In combination withαPD-L1,the antitumor effect was further enhanced.Therefore,NP/mDs provide a promising strategy for the comprehensive treatment of malignancy.
