Journal
CHEMICAL ENGINEERING JOURNAL
Volume 425, Issue -, Pages -Publisher
ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2021.131451
Keywords
Non-small cell lung cancer; Hydroxyl-radical nanogenerator; Chemotherapy; Immunotherapy
Categories
Funding
- National Natural Science Foundation of China [61805049]
- National Key Research and Development Program of China [2017YFA0205200]
- Guangdong Basic and Applied Basic Research Foundation [2020A1515011101, 2021A1515011703, 2020A1515010543]
- Guangxi Natural Science Foundation [2020JJB140044]
- Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi [20180071]
- Innovation Project of Guangxi Graduate Education [YCSW2020050]
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This study developed a novel nanocomplex that can deliver therapeutic cargos to tumors and enhance the chemotherapeutic efficacy by generating hydroxyl radicals through cascade reactions, as well as converting immunologically cold tumors to hot tumors by triggering immunogenic tumor cell death. The nanocomplexes show promise as a treatment strategy for NSCLC through combining targeted therapy and immunotherapy.
Non-small cell lung cancer (NSCLC) has a low response rates to platinum-based chemotherapy represented by cisplatin (CDDP), and the combination regimen of CDDP and immune checkpoint blockers (ICBs) has demonstrated limited therapeutic efficacy and increased side effects in clinical trials. In this study, we prepare a cancer cell membrane camouflaged-nanocomplex that precisely delivers CDDP and programmed death-ligand 1 (PD-L1)-targeted antagonistic DNA aptamers (Apt) to the tumor, and responsively releases therapeutic cargos and ferrous ions (Fe2+) accompanying with the degradation under the acidic tumor microenvironment. In addition to the chemotherapeutic effect, CDDP elevates the intracellular H2O2 level through cascade reactions, enabling the persistent conversion of H2O2 to highly cytotoxic center dot OH through the Fenton reaction between H2O2 and Fe2+, which endows the nanocomplexes with hydroxyl-radical-generation ability and enhances the chemotherapeutic efficacy. Notably, the nanocomplexes as hydroxyl-radical nanogenerators can reverse immunologically cold tumors to hot tumors by triggering immunogenic tumor cell death and enhance the therapeutic efficacy in combination with ICBs (Apt). Therefore, our study is expected to provide a reasonable treatment paradigm for NSCLC by utilizing the homologous-targeted and tumor microenvironment-activated hydroxyl radical nano-generator to enhance chemoimmunotherapy.
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