期刊
BIOMATERIALS
卷 177, 期 -, 页码 149-160出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.05.051
关键词
Gold/manganese dioxide nanocage; Hypoxia; Photodynamic therapy; Immunogenic cell death; Metastasis
资金
- National Natural Science Foundation of China [81701816, 81671758, 31571013, 51502333, 81501580]
- China Postdoctoral Science Foundation [2017M612776]
- Key International S&T Cooperation Project [2015DFH50230]
- Natural Science Foundation of Guangdong Province [2017A030313079, 2017A030313726]
- Guangdong Natural Science Foundation of Research Team [2016A030312006]
- Dongguan Project on Social Science and Technology Development [2015108101019]
- Shenzhen Science and Technology Program [JCYJ20170818162259843, JSGG20160331185422390, JCYJ20160429191503002]
- SLAT Innovation Program for Excellent Young Researchers [Y7G005]
Metastatic triple-negative breast cancer (mTNBC) is an aggressive disease among women worldwide, characterized by high mortality and poor prognosis despite systemic therapy with radiation and chemotherapies. Photodynamic therapy (PDT) is an important strategy to eliminate the primary tumor, however its therapeutic efficacy against metastases and recurrence is still limited. Here, we employed a template method to develop the core-shell gold nanocage@manganese dioxide (AuNC@MnO2, AM) nanoparticles as tumor microenvironment responsive oxygen producers and near-infrared (NIR)-triggered reactive oxygen species (ROS) generators for oxygen-boosted immunogenic PDT against mTNBC. In this platform, MnO2 shell degrades in acidic tumor microenvironment pH/H2O2 conditions and generates massive oxygen to boost PDT effect of AM nanoparticles under laser irradiation. Fluorescence (FL)/ photoacoustic (PA)/magnetic resonance (MR) multimodal imaging confirms the effective accumulation of AM nanoparticles with sufficient oxygenation in tumor site to ameliorate local hypoxia. Moreover, the oxygen-boosted PDT effect of AM not only destroys primary tumor effectively but also elicits immunogenic cell death (ICD) with damage-associated molecular patterns (DAMPS) release, which subsequently induces DC maturation and effector cells activation, thereby robustly evoking systematic antitumor immune responses against mTNBC. Hence, this oxygen-boosted immunogenic PDT nanosystem offers a promising approach to ablate primary tumor and simultaneously prevent tumor metastases via immunogenic abscopal effects. (C) 2018 Elsevier Ltd. All rights reserved.
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