Journal
ADVANCED MATERIALS
Volume 31, Issue 51, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201905271
Keywords
cancer metastasis inhibition; cascade reaction; immune system activation; PEGylated CMS@GOx; synergistic therapy
Categories
Funding
- Chinese Government [2017YFE0132300]
- Australian Government [2017YFE0132300]
- National Natural Science Foundation of China [NSFC 51672268, 51929201, 51972138, 51720105015, 51628201, 51828202, 81972918]
- Key Research Program of Frontier Sciences, CAS [YZDY-SSW-JSC018]
- Projects for Science and Technology Development Plan of Jilin province [20170414003GH, 20190201232JC]
- Overseas, Hong Kong & Macao Scholars Collaborated Researching Fund [51828202]
- Guangzhou key medical discipline construction project fund [CAS18204]
- CAS-Croucher Funding Scheme for Joint Laboratories [CAS18204]
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The unique tumor microenvironment (TME) facilitates cancer proliferation and metastasis, and it is hard to cure cancer completely via monotherapy. Herein, a multifunctional cascade bioreactor based on hollow mesoporous Cu2MoS4 (CMS) loaded with glucose oxidase (GOx) is constructed for synergetic cancer therapy by chemo-dynamic therapy (CDT)/starvation therapy/phototherapy/immunotherapy. The CMS harboring multivalent elements (Cu1+/2+, Mo4+/6+) exhibit Fenton-like, glutathione (GSH) peroxidase-like and catalase-like activity. Once internalized into the tumor, CMS could generate center dot OH for CDT via Fenton-like reaction and deplete overexpressed GSH in TME to alleviate antioxidant capability of the tumors. Moreover, under hypoxia TME, the catalase-like CMS could react with endogenous H2O2 to generate O-2 for activating the catalyzed oxidation of glucose by GOx for starvation therapy accompanied with the regeneration of H2O2. The regenerated H2O2 can devote to Fenton-like reaction for realizing GOx-catalysis-enhanced CDT. Meanwhile, the CMS under 1064 nm laser irradiation shows remarkable tumor-killing ability by phototherapy due to its excellent photothermal conversion efficiency (eta = 63.3%) and cytotoxic superoxide anion (center dot O-2(-)) generation performance. More importantly, the PEGylated CMS@GOx-based synergistic therapy combined with checkpoint blockade therapy could elicit robust immune responses for both effectively ablating primary tumors and inhibiting cancer metastasis.
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