Natural Cell-Inspired Integration of Redox Reactant Molecules in Hierarchical MOFs Harvested for Reaction Pathway-Regulated Glycoprotein Assay

Natural cell systems with multiple isolated compartments possess controllable signal transduction pathways, which can segregate a series of complex substances and confine them from each other to allow for feedback-driven reactions. By biomimicking the ingenuity of cell systems, we herein designed spatially compact metal–organic frameworks (MOFs) as a hierarchical host for complex substances at isolated locations for the development of reaction pathway-regulated glycoprotein assay. The well-defined zeolitic imidazolate framework-8 (ZIF-8) matrices were fabricated via epitaxial growth to organize the multishelled integration of multiple guest substances including redox reactant substrates (i.e., resazurin and amplex red) and Pt-shelled Au (AuPt) entities. In addition, the micropore nature and enclosed space of the ZIF-8 matrix can prohibit the surpassed contact between fluorogenic substrates and catalytic AuPt converters, inherently, while the immediate signal generator pattern can be harvested through textural collapse of the ZIF-8 skeleton in a controllable manner. Our proposed glycoprotein assay can be conducted with on-demand redox reactions for signal generators: a reductive N -deoxygenation of resazurin and an oxidative N -deacetylation of amplex red, respectively. Due to the distinct catalytic behavior of AuPt converters involved in the fluorogenic redox reactions, the detection limit of the reaction pathway-regulated glycoprotein assay can reach 14.27 pM for the reductive N- deoxygenation reaction and 71.63 pM for the oxidative N- deacetylation reaction, respectively. Collectively, our proposed method may offer an innovative inspiration of reaction pathway-regulated glycoprotein assay, and it can also be adapted for rational substitution of substrate molecules to broaden its signal reflections in versatile glycoprotein analysis.