Premium
Programmable Therapeutic Nanodevices with Circular Amplification of H 2 O 2 in the Tumor Microenvironment for Synergistic Cancer Therapy
Author(s) -
Li Jiong,
Wei Zuwu,
Lin Xinyi,
Zheng Dongye,
Wu Ming,
Liu Xiaolong,
Liu Jingfeng
Publication year - 2019
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201801627
Subject(s) - prodrug , tumor microenvironment , ethylene glycol , tumor hypoxia , hydrogen peroxide , cytotoxicity , catalysis , cancer research , biophysics , chemistry , combinatorial chemistry , glucose oxidase , materials science , biochemistry , tumor cells , biology , organic chemistry , enzyme , medicine , in vitro , radiation therapy
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 H 2 O 2 in tumor microenvironment to improve the permeability of membranes for glucose entrance. Afterward, the oxidation of glucose catalyzed by GOD produces amplified H 2 O 2 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 H 2 O 2 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.