Chen, YuhaoYuhaoChenGeng, XiaoruiXiaoruiGengRao, Ganipisetti HanumanthaGanipisetti HanumanthaRaoWei, Wei-ChihWei-ChihWeiVenkateswararao, AddankiAddankiVenkateswararaoLiu, Tzu-MingTzu-MingLiuWong, Ken-TsungKen-TsungWongLi, YunYunLiKe, Pu ChunPu ChunKeYuan, ZhenZhenYuan2025-08-202025-08-202025-09https://scholars.lib.ntu.edu.tw/handle/123456789/731537Although photothermal therapy (PTT) is a promising strategy for cancer treatment, the immunosuppressive tumor microenvironment promotes tumor progression and metastasis, limiting its effectiveness. To enhance adaptive antitumor immunity and improve post-PTT immunotherapy, genetically engineered bacteria outer membrane vesicles (OMVs)-modified small-molecule organic dye was constructed to serve as a nanophotosensitizer for NIR-II fluorescence/photoacoustic imaging-guided photo-immunotherapy. The developed nanophotosensitizer generated toxic hyperthermia under laser irradiation, promoting tumor antigen release. Meanwhile, the CD47nb-OMVs repolarized tumor-associated macrophages by blocking CD47-SIRRPα axis, relieving immunosuppressive tumor microenvironment. In addition, the present theranostic nanoplatform initiated tumor-resident type I conventional dendritic cells (cDC1s)-mediated antigen cross-presentation cascade, enhancing the downstream anti-tumor CD8+ T cell response. Furthermore, in vivo tests by using triple-negative breast cancer mouse model demonstrated that the novel NIR-II nanophotosensitizer effectively transformed the immunologically cold tumor microenvironment into a hot one, significantly improve survival rates, and inhibit distant metastases.enCD47Engineered bacteriaImmunotherapyNIR-II optical imagingOMV[SDGs]SDG3journal article10.1016/j.cej.2025.166083