School of Life Science, Beijing Institute of Technology, Beijing, 100081, P. R. China.
National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, P. R. China.
Adv Mater. 2021 Feb;33(7):e2005562. doi: 10.1002/adma.202005562. Epub 2021 Jan 12.
Extracellular vesicles (EVs) hold great potential in both disease treatment and drug delivery. However, accurate drug release from EVs, as well as the spontaneous treatment effect cooperation of EVs and drugs at target tissues, is still challenging. Here, an engineered self-activatable photo-EV for synergistic trimodal anticancer therapy is reported. M1 macrophage-derived EVs (M1 EVs) are simultaneously loaded with bis[2,4,5-trichloro-6-(pentyloxycarbonyl) phenyl] oxalate (CPPO), chlorin e6 (Ce6), and prodrug aldoxorubicin (Dox-EMCH). After administration, the as-prepared system actively targets tumor cells because of the tumor-homing capability of M1 EVs, wherein M1 EVs repolarize M2 to M1 macrophages, which not only display immunotherapy effects but also produce H O . The reaction between H O and CPPO generates chemical energy that activates Ce6, creating both chemiluminescence for imaging and singlet oxygen ( O ) for photodynamic therapy (PDT). Meanwhile, O -induced membrane rupture leads to the release of Dox-EMCH, which is then activated and penetrates the deep hypoxic areas of tumors. The synergism of immunotherapy, PDT, and chemotherapy results in potent anticancer efficacy, showing great promise to fight cancers.
细胞外囊泡 (EVs) 在疾病治疗和药物输送方面具有巨大的潜力。然而，从 EVs 中准确释放药物，以及 EVs 和药物在靶组织中的自发治疗效果协同作用，仍然具有挑战性。在此，报道了一种用于协同三模态抗癌治疗的工程化自激活光 EV。M1 巨噬细胞衍生的 EV (M1 EV) 同时负载双 [2,4,5-三氯-6-(戊氧基羰基)苯基] 草酸酯 (CPPO)、氯乙酮 (Ce6) 和前药阿霉素 (Dox-EMCH)。给药后，由于 M1 EV 的肿瘤归巢能力，所制备的系统主动靶向肿瘤细胞，其中 M1 EV 将 M2 重极化为 M1 巨噬细胞，这不仅显示出免疫治疗效果，还产生 H O 。H O 和 CPPO 之间的反应产生化学能量，激活 Ce6，产生用于成像的化学发光和用于光动力治疗 (PDT) 的单线态氧 ( O )。同时， O 诱导的膜破裂导致 Dox-EMCH 的释放，然后将其激活并穿透肿瘤的深部缺氧区域。免疫疗法、PDT 和化学疗法的协同作用产生了强大的抗癌疗效，为抗击癌症带来了巨大的希望。
