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Therapeutic Vesicular Nanoreactors with Tumor‐Specific Activation and Self‐Destruction for Synergistic Tumor Ablation
Author(s) -
Li Junjie,
Dirisala Anjaneyulu,
Ge Zhishen,
Wang Yuheng,
Yin Wei,
Ke Wendong,
Toh Kazuko,
Xie Jinbing,
Matsumoto Yu,
Anraku Yasutaka,
Osada Kensuke,
Kataoka Kazunori
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201706964
Subject(s) - chemistry , hydrogen peroxide , ethylene glycol , nanoreactor , in vivo , glutathione , methacrylate , glucose oxidase , biophysics , catalysis , combinatorial chemistry , polymerization , biochemistry , organic chemistry , enzyme , polymer , microbiology and biotechnology , biology
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 ( thera NR) 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, thera NR are inactive in normal tissues. At a tumor site, thera NR are specifically activated by the tumor acidity via improved permeability of the membranes. Hydrogen peroxide (H 2 O 2 ) production by the catalysis of GOD in thera NR increases tumor oxidative stress significantly. Meanwhile, high levels of H 2 O 2 induce self‐destruction of thera NR releasing quinone methide (QM) to deplete glutathione and suppress the antioxidant ability of cancer cells. Finally, thera NR efficiently kill cancer cells and ablate tumors via the synergistic effect.