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Plasmon‐Driven Catalytic Chemotherapy Augments Cancer Immunotherapy through Induction of Immunogenic Cell Death and Blockage of IDO Pathway
Author(s) -
Ding Yuan,
Sun Zhongquan,
Gao Yong,
Zhang Sitong,
Yang Caixia,
Qian Zhefeng,
Jin Lulu,
Zhang Jiaojiao,
Zeng Cheng,
Mao Zhengwei,
Wang Weilin
Publication year - 2021
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.202102188
Subject(s) - immunogenic cell death , immunotherapy , tumor microenvironment , cancer research , cancer immunotherapy , chemotherapy , prodrug , immunogenicity , cancer , cancer cell , medicine , immune system , immunology , materials science , pharmacology
Clinical trials confirm the combination of indoleamine 2,3‐dioxygenase (IDO) blockade and immunogenic chemotherapy represents a brilliant future in cancer therapy. However, it remains challenging to precisely activate chemo‐immunotherapy in situ to avoid side effects from the systemic administrations and reverse the poor immunogenicity and immunosuppressive microenvironment in tumor sites. Herein, a hybrid nanomedicine (“ RPMANB NPs ”) to co‐deliver an IDO inhibitor (NLG919) and a chemotherapeutic prodrug to amplify the therapeutic benefits are designed. Attributed to the delicate surface engineering, the RPMANB NPs possess excellent pharmacokinetics and tumor accumulation. The loaded NLG919 are released inside cancer tissues/cells due to the collapse of the metal–organic framework platform triggered by the highly concentrated phosphate, reversing the immunosuppressive tumor microenvironment by suppressing IDO activity. The potent chemotherapeutic drug is precisely activated through a highly efficient plasmon‐driven catalysis in the presence of near‐infrared light, eliciting antitumor immunity by triggering immunogenic cell death and avoiding side effects through in situ activation of chemotherapy. In vivo studies demonstrate that the chemo‐immunotherapy greatly suppresses the tumor growth by promoting intratumoral accumulation of cytotoxic T lymphocytes and downregulating regulatory T cells. This work establishes a robust delivery platform to overcome the current obstacles of tumor treatments by combining precisely activatable chemotherapy with immunotherapy.