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Responsive Exosome Nano‐bioconjugates for Synergistic Cancer Therapy
Author(s) -
Nie Weidong,
Wu Guanghao,
Zhang Jinfeng,
Huang LiLi,
Ding Jingjing,
Jiang Anqi,
Zhang Yahui,
Liu Yanhong,
Li Jingchao,
Pu Kanyi,
Xie HaiYan
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201912524
Subject(s) - cd47 , microvesicles , exosome , chemistry , tumor microenvironment , cancer cell , in vivo , cancer research , drug delivery , cancer therapy , microbiology and biotechnology , cancer , cell , biochemistry , tumor cells , biology , microrna , genetics , organic chemistry , gene
Exosomes hold great potential in therapeutic development. However, native exosomes usually induce insufficient effects in vivo and simply act as drug delivery vehicles. Herein, we synthesize responsive exosome nano‐bioconjugates for cancer therapy. Azide‐modified exosomes derived from M1 macrophages are conjugated with dibenzocyclooctyne‐modified antibodies of CD47 and SIRPα (aCD47 and aSIRPα) through pH‐sensitive linkers. After systemic administration, the nano‐bioconjugates can actively target tumors through the specific recognition between aCD47 and CD47 on the tumor cell surface. In the acidic tumor microenvironment, the benzoic‐imine bonds of the nano‐bioconjugates are cleaved to release aSIRPα and aCD47 that can, respectively, block SIRPα on macrophages and CD47, leading to abolished “don't eat me” signaling and improved phagocytosis of macrophages. Meanwhile, the native M1 exosomes effectively reprogram the macrophages from pro‐tumoral M2 to anti‐tumoral M1.