Therapeutic Vesicular Nanoreactors with Tumor-Specific Activation and Self-Destruction for Synergistic Tumor Ablation.
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 (H2 O2 ) production by the catalysis of GOD in theraNR increases tumor oxidative stress significantly. Meanwhile, high levels of H2 O2 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.
['Li|Junjie|J|', 'Dirisala|Anjaneyulu|A|', 'Ge|Zhishen|Z|', 'Wang|Yuheng|Y|', 'Yin|Wei|W|', 'Ke|Wendong|W|', 'Toh|Kazuko|K|', 'Xie|Jinbing|J|', 'Matsumoto|Yu|Y|', 'Anraku|Yasutaka|Y|', 'Osada|Kensuke|K|', 'Kataoka|Kazunori|K|']
D000970:Antineoplastic Agents D000975:Antioxidants D001897:Boronic Acids D016923:Cell Death D002463:Cell Membrane Permeability D004337:Drug Carriers D004952:Esters D005949:Glucose Oxidase D005978:Glutathione D006801:Humans D006861:Hydrogen Peroxide D006863:Hydrogen-Ion Concentration D045563:Indolequinones D008689:Methacrylates D046529:Microscopy, Electron, Transmission D049329:Nanostructures D009369:Neoplasms D010880:Piperidines D011092:Polyethylene Glycols D000075082:Proof of Concept Study
nanoreactors cancer therapy enzyme delivery membrane permeability polymersomes