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Dual Gate‐Controlled Therapeutics for Overcoming Bacterium‐Induced Drug Resistance and Potentiating Cancer Immunotherapy
Author(s) -
Zhang Xiaodong,
Chen Xiaokai,
Guo Yuxin,
Gao Ge,
Wang Dongdong,
Wu Yinglong,
Liu Jiawei,
Liang Gaolin,
Zhao Yanli,
Wu FuGen
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202102059
Subject(s) - bacteria , tumor microenvironment , immune system , drug resistance , hyaluronidase , immunotherapy , cancer research , cancer cell , cancer immunotherapy , microbiology and biotechnology , drug , chemistry , cancer , biology , enzyme , pharmacology , immunology , biochemistry , genetics
The presence of bacteria in the tumor can cause cancer resistance to chemotherapeutics. To fight against bacterium‐induced drug resistance, herein we design self‐traceable nanoreservoirs that are simultaneously loaded with gemcitabine (an anticancer drug) and ciprofloxacin (an antibiotic) and are decorated with hyaluronic acid for active tumor targeting. The nanoreservoirs have a pH‐sensitive gate and an enzyme‐responsive gate that can be opened in the acidic and hyaluronidase‐abundant tumor microenvironment to control drug release rates. Moreover, the nanoreservoirs can specifically target the tumor regions without eliciting evident toxicity to normal tissues, kill the intratumoral bacteria, and inhibit the tumor growth even in the presence of the bacteria. Unexpectedly, the nanoreservoirs can activate T cell‐mediated immune responses through promoting antigen‐presenting dendritic cell maturation and depleting immunosuppressive myeloid‐derived suppressor cells in bacterium‐infected tumors.