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On‐Demand Autophagy Cascade Amplification Nanoparticles Precisely Enhanced Oxaliplatin‐Induced Cancer Immunotherapy
Author(s) -
Wang Xuhui,
Li Man,
Ren Kebai,
Xia Chunyu,
Li Jianping,
Yu Qianwen,
Qiu Yue,
Lu Zhengze,
Long Yang,
Zhang Zhirong,
He Qin
Publication year - 2020
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.202002160
Subject(s) - autophagy , chemoimmunotherapy , programmed cell death , immunogenic cell death , immune system , cancer research , oxaliplatin , cancer cell , immunotherapy , materials science , tumor microenvironment , cancer immunotherapy , cancer , microbiology and biotechnology , biology , medicine , immunology , apoptosis , biochemistry , colorectal cancer
Chemoimmunotherapy‐induced antitumor immune response is highly dependent on tumor autophagy. When tumor cells are treated with chemoimmunotherapy, timely overactivated autophagy can not only lead more tumor cells to death, but also participate in the endogenous antigen presentation and immune stimulators secretion of dying cells, thus plays a vital role. However, timely and accurately overactivated tumor autophagy during chemoimmunotherapy is of great difficulty. Here, an on‐demand autophagy cascade amplification nanoparticle (ASN) is reported to boost oxaliplatin‐induced cancer immunotherapy. ASN is prepared by self‐assemble of autophagy‐responsible C‐TFG micelle and is followed by electrostatic binding of oxaliplatin prodrug (HA‐OXA). After entering tumor cells, the HA‐OXA shell of ASN first responds to the reduction microenvironment and releases oxaliplatin to trigger tumor immunogenic cell death and mildly stimulates tumor autophagy. Then, the exposed C‐TFG micelle can sensitively respond to oxaliplatin‐induced autophagy and release a powerful autophagy inducer STF‐62247, which precisely transforms autophagy to “overactivated” condition, leading tumor cells to autophagic death and enhance subsequent tumor antigen processing of the dying cells. In CT26 tumor‐bearing mice, ASN exhibits optimal immune stimulation and antitumor efficiency due to its on‐demand autophagy induction ability.