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Biomimetic enzyme cascade reaction system in microfluidic electrospray microcapsules.

ABSTRACT: Mimicking subcellular compartments containing enzymes in organisms is considered a promising approach to substitute for missing or lost cellular functions. Inspired by the multicompartment structures of cellular architectures, we present a novel multienzyme system based on hollow hydrogel microcapsules with flexible enzymatic inverse opal particles. Benefiting from the precise operation capability of the microfluidic electrospray and the remarkable structural color marks in the inverse opal particles, we developed a multienzyme system with controllable number, type, and spatial arrangement of the encapsulated enzymes. The hydrogel shells also could improve enzyme stability against proteolysis in the system. The multienzyme system containing alcohol oxidase and catalase could act as a cascade biocatalyst and reduce alcohol levels in media, providing an alternative antidote and prophylactic for alcohol intoxication. These features indicated that our strategy provides an ideal enzyme cascade reaction system for complex biocatalysis and biomimetic functions of some organelles or organs.

SUBMITTER: Wang H

PROVIDER: S-EPMC6003728 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Biomimetic enzyme cascade reaction system in microfluidic electrospray microcapsules.

Wang Huan H Zhao Ze Z Liu Yuxiao Y Shao Changmin C Bian Feika F Zhao Yuanjin Y

Science advances 20180615 6

Mimicking subcellular compartments containing enzymes in organisms is considered a promising approach to substitute for missing or lost cellular functions. Inspired by the multicompartment structures of cellular architectures, we present a novel multienzyme system based on hollow hydrogel microcapsules with flexible enzymatic inverse opal particles. Benefiting from the precise operation capability of the microfluidic electrospray and the remarkable structural color marks in the inverse opal part ...[more]

PMID: 29922720

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Project description:Although the enzyme catalytic nanoreactors reported so far have achieved excellent therapeutic efficacy, how to accurately exert enzyme activity in the tumor microenvironment to specifically kill tumor cells and avoid systemic oxidative damage would be an inevitable challenge for catalytic nanomedicine. At the present study, we fabricate an advanced biomimetic nanoreactor, SOD-Fe0@Lapa-ZRF for tumor multi-enzyme cascade delivery that combined specifically killing tumor cells and protect cells from oxidative stress. Methods: We first synthesized the FeNP-embedded SOD (SOD-Fe0) by reduction reaction using sodium borohydride. Next, SOD-Fe0 and Lapa cargo were encapsulated in ZIF-8 by self-assembly. In order to protect the cargo enzyme from digestion by protease and prolong blood circulating time, SOD-Fe0@Lapa-Z was further cloaked with RBC membrane and functionalized with folate targeting, resulting in the final advanced biomimetic nanoreactor SOD-Fe0@Lapa-ZRF. Results: Once internalized, ZIF-8 achieves pH-triggered disassembly in weakly acidic tumor microenvironment. The released SOD-Fe0 and Lapa were further endocytosed by tumor cells and the Lapa produces superoxide anion (O2 -•) through the catalysis of NQO1 that is overexpressed in tumor cells, while O2 -• is converted to H2O2 via SOD. At this time, the released ferrous ions from SOD-Fe0 and H2O2 are further transformed to highly toxic hydroxyl radicals (•OH) for specifically killing tumor cells, and there was no obvious toxicological response during long-term treatment. Importantly, SOD-Fe0@Lapa-ZRF enhanced the normal cell's anti-oxidation ability, and thus had little effect on the secretion of TNF-?, IL-6 and IL-1? pro-inflammatory cytokines, while effectively reversed the decreased activity of T-SOD and GSH-Px and remained stable MDA content after tumor treatment. In vitro and in vivo results indicate that the tumor microenvironment-responsive release multi-enzyme cascade have high tumor specificity and effective anti-tumor efficacy, and can protect cells from oxidative stress damage. Conclusion: The biomimetic nanoreactor will have a great potential in cancer nanomedicine and provide a novel strategy to regulate oxidative stress.

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Biomimetic enzyme cascade reaction system in microfluidic electrospray microcapsules.

Publications

Biomimetic enzyme cascade reaction system in microfluidic electrospray microcapsules.

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