Dual-Surfactant-Directed Mesoporous Metal-Alkyl-Thiol Frameworks for Enzyme-Au Nanoparticle-Coupled SERS Biosensing

It is desirable yet challenging to introduce highly active alkyl thiols into hierarchically porous (HP) metal-organic frameworks. Herein, we developed a dual-surfactant co-templating strategy to construct Zr-based HP metal-alkyl-thiol frameworks (HPMATFs), where the HP structure facilitated the encapsulation of bulky biomacromolecules while the integrated alkyl thiols greatly enhanced their affinity toward noble metals. The high density of hydrophilic moieties at the periphery of the composite micelles effectively anchored the Zr precursors, preventing phase separation and enabling precise control over the mesopore sizes from 3 to 40 nm. The abundant alkyl thiols in the framework enabled the successful introduction of uniformly dispersed gold nanoparticles (AuNPs) within the HPMATFs matrix. Such integration provided abundant plasmonic sites and open mesospaces for the free diffusion of target analytes, forming an effective surface-enhanced Raman scattering (SERS) platform. Spatial co-confinement of oxidases and the SERS probe ensured an immediate cascade reaction between proximal enzyme-generated products and the SERS probe anchored on AuNPs, realizing specific and sensitive recognition of the substrate of the applied enzymes. By altering the loaded enzymes, such a sensory platform can be applied for the specific detection of diverse biomolecular targets, prefiguring their potential for point-of-care diagnostics.