Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 25, Pages 14013-14021Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202102059
Keywords
bacterial infection; cancer therapy; drug resistance; dual stimulus responsiveness; immunotherapy
Categories
Funding
- National Natural Science Foundation of China [21673037]
- Fundamental Research Funds for the Central Universities
- Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant [A20E5c0081]
- Singapore Academic Research Fund [RT12/19]
- Singapore National Research Foundation Investigatorship [NRF-NRFI2018-03]
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Self-traceable nanoreservoirs loaded with both anticancer drug and antibiotic can target and kill intratumoral bacteria, inhibit tumor growth, and activate T cell-mediated immune responses. This therapy shows great potential for application in cancer treatment.
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.
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