Therapeutic Vesicular Nanoreactors with Tumor-Specific Activation and Self-Destruction for Synergistic Tumor Ablation.

Therapeutic Vesicular Nanoreactors with Tumor-Specific Activation and Self-Destruction for Synergistic Tumor Ablation.

Angew Chem Int Ed Engl. 2017 Sep 20;:

Authors: Li J, Dirisala A, Ge Z, Wang Y, Yin W, Ke W, Toh K, Xie J, Matsumoto Y, Anraku Y, Osada K, Kataoka K

Abstract
Polymeric nanoreactors (NRs) have distinct advantages to improve chemical reaction efficiency, but the in vivo applications were limited by lack of tissue-specificity. Herein, novel glucose oxidase (GOD)-loaded therapeutic vesicular NRs (theraNR) are constructed based on the diblock copolymer containing poly(ethylene glycol) (PEG) and copolymerized phenylboronic ester or piperidine-functionalized methacrylate (P(PBEM-co-PEM)). Upon systemic injection, theraNR keep inactive in normal tissues. At tumor site, theraNR are specifically activated by 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 level of H2O2 induces self-destruction of theraNR releasing quinone methide (QM) to deplete glutathione and suppress antioxidant ability of cancer cells. Finally, theraNR efficiently kill cancer cells and ablate tumor via the synergistic effect.

PMID: 28940903 [PubMed - as supplied by publisher]

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