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A Biomimetic Plasmonic Nanoreactor for Reliable Metabolite Detection.

ABSTRACT: Reliable monitoring of metabolites in biofluids is critical for diagnosis, treatment, and long-term management of various diseases. Although widely used, existing enzymatic metabolite assays face challenges in clinical practice primarily due to the susceptibility of enzyme activity to external conditions and the low sensitivity of sensing strategies. Inspired by the micro/nanoscale confined catalytic environment in living cells, the coencapsulation of oxidoreductase and metal nanoparticles within the nanopores of macroporous silica foams to fabricate all-in-one bio-nanoreactors is reported herein for use in surface-enhanced Raman scattering (SERS)-based metabolic assays. The enhancement of catalytical activity and stability of enzyme against high temperatures, long-time storage or proteolytic agents are demonstrated. The nanoreactors recognize and catalyze oxidation of the metabolite, and provide ratiometric SERS response in the presence of the enzymatic by-product H2O2, enabling sensitive metabolite quantification in a "sample in and answer out" manner. The nanoreactor makes any oxidoreductase-responsible metabolite a candidate for quantitative SERS sensing, as shown for glucose and lactate. Glucose levels of patients with bacterial infection are accurately analyzed with only 20 µL of cerebrospinal fluids, indicating the potential application of the nanoreactor in vitro clinical testing.

SUBMITTER: Liu J

PROVIDER: S-EPMC7237842 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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A Biomimetic Plasmonic Nanoreactor for Reliable Metabolite Detection.

Liu Jiangang J Cai Chenlei C Wang Yuning Y Liu Yu Y Huang Lin L Tian Tongtong T Yao Yuanyuan Y Wei Jia J Chen Ruoping R Zhang Kun K Liu Baohong B Qian Kun K

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200311 10

Reliable monitoring of metabolites in biofluids is critical for diagnosis, treatment, and long-term management of various diseases. Although widely used, existing enzymatic metabolite assays face challenges in clinical practice primarily due to the susceptibility of enzyme activity to external conditions and the low sensitivity of sensing strategies. Inspired by the micro/nanoscale confined catalytic environment in living cells, the coencapsulation of oxidoreductase and metal nanoparticles withi ...[more]

PMID: 32440487

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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-α, IL-6 and IL-1β 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.

Dataset Information

A Biomimetic Plasmonic Nanoreactor for Reliable Metabolite Detection.

Publications

A Biomimetic Plasmonic Nanoreactor for Reliable Metabolite Detection.

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