期刊
ACS NANO
卷 13, 期 4, 页码 4267-4277出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b09387
关键词
Fenton reaction; glutathione; chemodynamic therapy; cell membrane; photodynamic therapy
类别
资金
- National Natural Science Foundation of China [21874008, 21475008]
- Special Foundation for State Major Research Program of China [2016YFC0106602, 2016YFC0106601]
- Open Research Fund Program of Beijing Key Lab of Plant Resource Research and Development, Beijing Technology and Business University [PRRD-2016-YB2]
- Fundamental Research Funds for the Central Universities [FRF-BD-17-016A]
- Beijing Municipal Science and Technology Commission [z131102002813058]
The integration of reactive oxygen species (ROS)-involved photodynamic therapy (PDT) and chemo-dynamic therapy (CDT) holds great promise for enhanced anticancer effects. Herein, we report biodegradable cancer cell membrane-coated mesoporous copper/manganese silicate nanospheres (mCMSNs) with homotypic targeting ability to the cancer cell lines and enhanced ROS generation through singlet oxygen (O-1(2)) production and glutathione (GSH)-activated Fenton reaction, showing excellent CDT/PDT synergistic therapeutic effects. We demonstrate that mCMSNs are able to relieve the tumor hypoxia microenvironment by catalytic decomposition of endogenous H2O2 to O-2 and further react with O-2 to produce toxic O-1(2) with a 635 nm laser irradiation. GSH-triggered mCMSNs biodegradation can simultaneously generate Fenton-like Cu+ and Mn2+ ions and deplete GSH for efficient hydroxyl radical (center dot OH) production. The specific recognition and homotypic targeting ability to the cancer cells were also revealed. Notably, relieving hypoxia and GSH depletion disrupts the tumor microenvironment (TME) and cellular antioxidant defense system, achieving exceptional cancer targeting therapeutic effects in vitro and in vivo. The cancer cells growth was significantly inhibited. Moreover, the released Mn2+ can also act as an advanced contrast agent for cancer magnetic resonance imaging (MRI). Thus, together with photosensitizers, Fenton agent provider and MRI contrast effects along with the modulating of the TME allow mCMSNs to realize MRI-monitored enhanced CDT/PDT synergistic therapy. It provides a paradigm to rationally design TME-responsive and ROS-involved therapeutic strategies based on a single polymetallic silicate nanomaterial with enhanced anticancer effects.
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