Dual gate-controlled therapeutics for overcoming bacterium-induced drug resistance and potentiating cancer immunotherapy

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 de...

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Main Authors: Zhang, Xiaodong, Chen, Xiaokai, Guo, Yuxin, Gao, Ge, Wang, Dongdong, Wu, Yinglong, Liu, Jiawei, Liang, Gaolin, Zhao, Yanli, Wu, Fu-Gen
Other Authors: School of Physical and Mathematical Sciences
Format: Article
Language:English
Published: 2022
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Online Access:https://hdl.handle.net/10356/162861
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1628612022-11-11T04:22:41Z Dual gate-controlled therapeutics for overcoming bacterium-induced drug resistance and potentiating cancer immunotherapy Zhang, Xiaodong Chen, Xiaokai Guo, Yuxin Gao, Ge Wang, Dongdong Wu, Yinglong Liu, Jiawei Liang, Gaolin Zhao, Yanli Wu, Fu-Gen School of Physical and Mathematical Sciences Science::Chemistry Bacterial Infection Cancer Therapy 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. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) This work was supported by the National Natural Science Foundation of China (21673037) and the Fundamental Research Funds for the Central Universities. It is also supported by the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A20E5c0081),the SingaporeAcademicResearchFund (RT12/19),and the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03). 2022-11-11T04:22:41Z 2022-11-11T04:22:41Z 2021 Journal Article Zhang, X., Chen, X., Guo, Y., Gao, G., Wang, D., Wu, Y., Liu, J., Liang, G., Zhao, Y. & Wu, F. (2021). Dual gate-controlled therapeutics for overcoming bacterium-induced drug resistance and potentiating cancer immunotherapy. Angewandte Chemie International Edition, 60(25), 14013-14021. https://dx.doi.org/10.1002/anie.202102059 1433-7851 https://hdl.handle.net/10356/162861 10.1002/anie.202102059 33768682 2-s2.0-85105431724 25 60 14013 14021 en A20E5c0081 RT12/19 NRF-NRFI2018-03 Angewandte Chemie International Edition © 2021 Wiley-VCH GmbH. All rights reserved.
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Chemistry
Bacterial Infection
Cancer Therapy
spellingShingle Science::Chemistry
Bacterial Infection
Cancer Therapy
Zhang, Xiaodong
Chen, Xiaokai
Guo, Yuxin
Gao, Ge
Wang, Dongdong
Wu, Yinglong
Liu, Jiawei
Liang, Gaolin
Zhao, Yanli
Wu, Fu-Gen
Dual gate-controlled therapeutics for overcoming bacterium-induced drug resistance and potentiating cancer immunotherapy
description 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.
author2 School of Physical and Mathematical Sciences
author_facet School of Physical and Mathematical Sciences
Zhang, Xiaodong
Chen, Xiaokai
Guo, Yuxin
Gao, Ge
Wang, Dongdong
Wu, Yinglong
Liu, Jiawei
Liang, Gaolin
Zhao, Yanli
Wu, Fu-Gen
format Article
author Zhang, Xiaodong
Chen, Xiaokai
Guo, Yuxin
Gao, Ge
Wang, Dongdong
Wu, Yinglong
Liu, Jiawei
Liang, Gaolin
Zhao, Yanli
Wu, Fu-Gen
author_sort Zhang, Xiaodong
title Dual gate-controlled therapeutics for overcoming bacterium-induced drug resistance and potentiating cancer immunotherapy
title_short Dual gate-controlled therapeutics for overcoming bacterium-induced drug resistance and potentiating cancer immunotherapy
title_full Dual gate-controlled therapeutics for overcoming bacterium-induced drug resistance and potentiating cancer immunotherapy
title_fullStr Dual gate-controlled therapeutics for overcoming bacterium-induced drug resistance and potentiating cancer immunotherapy
title_full_unstemmed Dual gate-controlled therapeutics for overcoming bacterium-induced drug resistance and potentiating cancer immunotherapy
title_sort dual gate-controlled therapeutics for overcoming bacterium-induced drug resistance and potentiating cancer immunotherapy
publishDate 2022
url https://hdl.handle.net/10356/162861
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