Journal
ACS NANO
Volume 15, Issue 10, Pages 16934-16945Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.1c08026
Keywords
antitumor therapy; lactic acid; metal-phenolic network; sonodynamic therapy; tumor microenvironment
Categories
Funding
- National Natural Science Foundation of China (NSFC) [32171318, 32101069]
- Faculty of Health Sciences, University of Macau
- Start-up Research Grant (SRG) of University of Macau [SRG2018-00130-FHS]
- Science and Technology Development Fund, Macau SAR [0109/2018/A3, 0011/2019/AKP]
- Shenzhen Science and Technology Innovation Commission, Shenzhen-Hong Kong-Macau Science and Technology Plan C [SGDX20201103093600004]
- Proteomics, Metabolomics and Drug Development Core
- Animal Research Core
- Biological Imaging and Stem Cell Core in the Faculty of Health Sciences, University of Macau
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The constructed nanocomplex can remodel the immunosuppressive tumor microenvironment and achieve effective inhibition of tumors through sonodynamic therapy, while alleviating tumor hypoxia and acidic environment.
Nanomedicine has revolutionized cancer therapeutic strategies but has not completely changed the outcomes of tricky tumors that evolve a sophisticated immunosuppressive tumor microenvironment (TME) such as acidification. Here, a metal-phenolic network-based nanocomplex embedded with lactate oxidase (LOX) and a mitochondrial respiration inhibitor atovaquone (ATO) was constructed for immunosuppressive TME remodeling and sonodynamic therapy (SDT). In this nanocomplex, the sonosensitizer chlorin e6-conjugated polyphenol derivative can induce the generation of tumor lethal reactive oxygen species upon ultrasound irradiation. LOX served as a catalyst for intracellular lactic acid exhaustion, and ATO led to mitochondrial dysfunction to decrease oxygen consumption. This nanocomplex reversed the tumor immunosuppressive status by alleviating tumor hypoxia and acidic TME, achieving the characteristic enhancement of SDT and the inhibition of tumor proliferation and metastasis.
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