Single cell sequencing after sonodynamic therapy

Low tumor mutational burden and absence of T cells within the tumor sites are typical characteristics of "cold immune tumors" that paralyze the immune system. The strategy of reversing "cold tumors" to "hot tumors" infiltrated a high degree of T cells to activate antitumor immunity has attracted lots of attention. Herein, we encapsulated mesoporous dopamine with M1 macrophage-derived vesicles and loaded them with the fluorescent dye Indocyanine Green (ICG) core-shell MPDA /ICG@M1NVs NPs to realize nanoparticles-mediated local photothermal-triggered immunotherapy. As expected, MPDA/ICG core integrates dual Phototherapy of photodynamic therapy and photothermal therapy, thus enhancing cancer cell apoptosis by producing higher hyperthermia. The results of in vitro and vivo experiments demonstrate that the synergy between M1NVs mediated immunotherapy and MPDA/ICG -induced Phototherapy generated a localized antitumor-immune response with an excellent cancer-killing effect under the presence of tumor-associated antigens. At the same time, the addition of ICG brings dual-mode imaging of tumor fluorescence imaging and photoacoustic imaging to realize the early detection and diagnosis of liver cancer cells.

肿瘤突变负荷低下且肿瘤灶内缺乏T细胞，是麻痹免疫系统的“冷免疫肿瘤（cold immune tumors）”的典型特征。将“冷肿瘤”转化为可浸润大量T细胞以激活抗肿瘤免疫的“热肿瘤”的策略，已受到广泛关注。本研究中，我们以M1型巨噬细胞来源囊泡（M1 macrophage-derived vesicles）包裹介孔多巴胺（mesoporous dopamine），并负载荧光染料吲哚菁绿（Indocyanine Green, ICG），构建核壳结构MPDA/ICG@M1NVs纳米颗粒，以实现纳米颗粒介导的局部光热触发免疫治疗。如预期所示，MPDA/ICG核可整合光动力治疗（photodynamic therapy）与光热治疗（photothermal therapy）的双重光疗功能，通过产生更高强度的热疗效应促进癌细胞凋亡。体外与体内实验结果表明，在肿瘤相关抗原（tumor-associated antigens）存在的条件下，M1NVs介导的免疫治疗与MPDA/ICG诱导的光疗协同作用，可产生局部抗肿瘤免疫应答，展现出优异的抗癌效应。与此同时，ICG的引入可实现肿瘤荧光成像与光声成像的双模态成像，进而完成肝癌细胞的早期检测与诊断。