Programmable Therapeutic Nanodevices with Circular Amplification of H2O2 in the Tumor Microenvironment for Synergistic Cancer Therapy. Issue 10 (3rd April 2019)

• Record Type: Journal Article
• Authors: Li, Jiong; Wei, Zuwu; Lin, Xinyi; Zheng, Dongye; Wu, Ming; Liu, Xiaolong; Liu, Jingfeng
• Is Part Of: Advanced healthcare materials. Volume 8:Issue 10(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-04-03
• Subjects: AQ4N -- glucose oxidase -- H2O2 circular amplification -- H2O2‐responsiveness -- synergistic cancer therapy; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201801627
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: Tumor microenvironment activated nanodevices have remarkable superiority to enhance therapeutic efficacy and minimize side effects, but their practical applications are dramatically reduced by the low abundance and heterogeneous distribution of specific stimuli at the tumor site. Herein, programmable vesicular nanodevices based on the triblock copolymer containing poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) with peroxalate esters (PO) as hydrogen peroxide‐responsive linkage (PEG‐PO‐PCL‐PO‐PEG), are developed for co‐delivery of hypoxia‐activated prodrug (AQ4N) and glucose oxidase (GOD). The obtained nanodevices (PAG) can be activated by the high level of H2 O2 in tumor microenvironment to improve the permeability of membranes for glucose entrance. Afterward, the oxidation of glucose catalyzed by GOD produces amplified H2 O2 amounts which in turn induce complete destruction of PAG for fast release of AQ4N and GOD. Ultimately, the PAG can exert programmable therapeutic effects from the following aspects: 1) starvation therapy by cutting off the energy supply from glucose through GOD catalysis; 2) oxidative cytotoxicity after H2 O2 amplification; 3) chemotherapy of AQ4N activated by the intensified tumor hypoxia microenvironment after oxygen consumption. The stimuli amplification, controlled drug release, synergistic therapy, and corresponding mechanisms of PAG are demonstrated. Therefore, the presented work could provide significant new insights for cancer treatment. Abstract : A nanodevice (PAG) with tumor‐specific H2 O2 activation and circular amplification abilities is reported. PAG can be selectively activated by the high level of H2 O2 in the tumor microenvironment to boost glucose oxidase and AQ4N release, which ultimately exert synergistic starvation therapy, oxidative damage, and chemotherapy with an intrinsic "logic" relationship.