摘要Postoperative tumor recurrence remains a predominant cause of treatment failure.In this study,we developed an in situ injectable hydrogel,termed MPB-NO@DOX+ATRA gel,which was locally formed within the tumor resection cavity.The MPB-NO@DOX+ATRA gel was fabricated by mixing a thrombin solution,a fibrinogen solution containing all-trans retinoic acid(ATRA),and a Mn/NO-based immune nano-activator termed MPB-NO@DOX.ATRA promoted the differentiation of cancer stem cells,inhibited cancer cell migration,and affected the polarization of tumor-associated macrophages.The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+and produce O2,resulting in the release of doxorubicin(DOX).The released DOX entered the nucleus and destroyed DNA,and the fragmented DNA cooperated with Mn2+to activate the cGAS-STING pathway and stimulate an anti-tumor immune response.In addition,when MPB-NO@DOX was exposed to 808 nm laser irradiation,the Fe-NO bond was broken to release NO,which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment.In conclusion,the MPB-NO@DOX+ATRA gel exhibited excellent anti-tumor efficacy.The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.