Programmable Modular Assembly of Functional Proteins on Raman-Encoded Zeolitic Imidazolate Framework-8 (ZIF-8) Nanoparticles as SERS Tags

Zeolitic imidazolate framework-8 (ZIF-8) is a metal organic framework with exceptional intrinsic properties, high tunability, cost effectiveness, and producibility, which has boosted the research development of the field. ZIF-8-based materials have shown high capabilities for multiple purposes as catalysts, capacitors, electrodes, drug delivery systems, or adsorption/separation membranes. Herein, we report the synergistic combination of ZIF-8, plasmonic nanoparticles, and rationally designed protein adaptors and antibodies for fabricating novel surface-enhanced Raman scattering (SERS) tags with enhanced sensing capabilities. The SERS tags consist of Au@Ag core-shell nanorods individually encapsulated within a multifunctional ZIF-8 matrix encoded with Raman reporters. While the role of the plasmonic core is to enhance the Raman, the ZIF-8 traps the Raman active molecules and, more importantly, facilitates the active targeting of the SERS tag surface through the modular assembly with conventional (i.e., immunoglobulins) and recombinant antibodies (i.e., nanobodies) mediated by the specific interaction of Zn2+ with polyhistidine-tagged protein G and SpyCatcher. Evidence of the capabilities of the Au@Ag@ZIF-8 nanotags for the SERS detection of EGFR and CD44 cell surface receptors in vitro illustrates the potential of these optical nanoprobes for imaging and multiplex biodetection. The reported modular assembly approach for the functionalization of ZIF-8 SERS nanotags with different classes of antibodies based on polyhistidinetagged peptides and protein-protein interactions can not only be applied to the ever-increasing number of reported MOFs structures but also can be further exploited as a universal means for the functionalization of other transition metal surfaces.