期刊
ADVANCED SCIENCE
卷 9, 期 36, 页码 -出版社
WILEY
DOI: 10.1002/advs.202203263
关键词
chemoradiotherapy; cooperative therapy; head and neck cancer; immune evasion; immunogenic cell death
资金
- National Natural Science Foundation of China [51873228, 52003194, 82102915]
- Science Foundation of Shanghai Science and Technology Commission [20430711800, 21ZR1437900]
- China Postdoctoral Science Foundation [2021M700157]
- Shanghai Post-Doctoral Excellence Program [2021424]
- Lingang Laboratory [LG-QS-202206-04]
- Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences [2019-027]
- biobank program of Shanghai Ninth people's hospital [YBKA201905]
This study presents a self-cooperative prodrug nanovesicle for highly tumor-specific chemoradiotherapy, which can target tumors efficiently and overcome immune evasion mechanisms.
Chemoradiotherapy is the standard of care for the clinical treatment of locally advanced head and neck cancers. However, the combination of ion radiation with free chemotherapeutics yields unsatisfactory therapeutic output and severe side effects due to the nonspecific biodistribution of the anticancer drugs. Herein, a self-cooperative prodrug nanovesicle is reported for highly tumor-specific chemoradiotherapy. The nanovesicles integrating a prodrug of oxaliplatin (OXA) can passively accumulate at the tumor site and penetrate deep into the tumor mass via matrix metalloproteinase 2-mediated cleavage of the polyethylene glycol corona. The OXA prodrug can be restored inside the tumor cells with endogenous glutathione to trigger immunogenic cell death (ICD) of the tumor cells and sensitize the tumor to ion radiation. The nanovesicles can be further loaded with the JAK inhibitor ruxolitinib to abolish chemoradiotherapy-induced programmed death ligand 1 (PD-L1) upregulation on the surface of the tumor cells, thereby prompting chemoradiotherapy-induced immunotherapy by blocking the interferon gamma-Janus kinase-signal transducer and activator of transcription axis. The prodrug nanoplatform reported herein might present a novel strategy to cooperatively enhance chemoradiotherapy of head and cancer and overcome PD-L1-dependent immune evasion.
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