期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 56, 期 45, 页码 14025-14030出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201706964
关键词
cancer therapy; enzyme delivery; membrane permeability; nanoreactors; polymersomes
资金
- National Natural Scientific Foundation of China (NNSFC) Project [21674104]
- Fundamental Research Funds for the Central Universities [WK3450000002]
- Grants-in-Aid for Scientific Research [16H03178, 15K12536, 25000006, 16K11226, 17KT0048] Funding Source: KAKEN
Polymeric nanoreactors (NRs) have distinct advantages to improve chemical reaction efficiency, but the in vivo applications are limited by lack of tissue-specificity. Herein, novel glucose oxidase (GOD)-loaded therapeutic vesicular NRs (theraNR) are constructed based on a diblock copolymer containing poly(ethylene glycol) (PEG) and copolymerized phenylboronic ester or piperidine-functionalized methacrylate (P(PBEM-co-PEM)). Upon systemic injection, theraNR are inactive in normal tissues. At a tumor site, theraNR are specifically activated by the tumor acidity via improved permeability of the membranes. Hydrogen peroxide (H2O2) production by the catalysis of GOD in theraNR increases tumor oxidative stress significantly. Meanwhile, high levels of H2O2 induce self-destruction of theraNR releasing quinone methide (QM) to deplete glutathione and suppress the antioxidant ability of cancer cells. Finally, theraNR efficiently kill cancer cells and ablate tumors via the synergistic effect.
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