Self-Activatable Photo-Extracellular Vesicle for Synergistic Trimodal Anticancer Therapy
Self-Activatable Photo-Extracellular Vesicle for Synergistic Trimodal Anticancer Therapy
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用于协同三模式抗癌治疗的自激活光细胞外囊泡
DOI：
10.1002/adma.202005562
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发表时间：
2021-01-12
影响因子：
29.4
通讯作者：
Xie, Hai-Yan
中科院分区：
文献类型：
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作者：
Ding, Jingjing;Lu, Guihong;Xie, Hai-Yan
细胞外囊泡（EVs）在疾病治疗和药物传递方面都具有巨大的潜力。然而，如何准确地从ev中释放药物，以及ev与药物在靶组织的自发治疗效果协同，仍然是一个挑战。本文报道了一种用于协同三峰抗癌治疗的工程自激活光ev。M1巨噬细胞衍生的ev （M1 ev）同时装载二[2,4,5-三氯-6-（戊氧羰基）苯基]草酸盐（CPPO）、氯e6 （Ce6）和前药醛多柔比星（Dox-EMCH）。给药后，由于M1 ev的归巢能力，制备的系统主动靶向肿瘤细胞，其中M1 ev将M2再极化为M1巨噬细胞，不仅具有免疫治疗作用，而且产生H2O2。H2O2和CPPO之间的反应产生激活Ce6的化学能，产生用于成像的化学发光和光动力治疗（PDT）的单线态氧（O-1(2)）。同时，O-1(2)诱导的膜破裂导致Dox-EMCH释放，Dox-EMCH被激活并渗透到肿瘤深部缺氧区。免疫疗法、PDT和化疗的协同作用产生了强大的抗癌功效，显示出对抗癌症的巨大希望。
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 H2O2. The reaction between H2O2 and CPPO generates chemical energy that activates Ce6, creating both chemiluminescence for imaging and singlet oxygen (O-1(2)) for photodynamic therapy (PDT). Meanwhile, O-1(2)-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.