Multifunctional Nanoparticles by Coordinative Self-Assembly of His-Tagged Units with Metal–Organic Frameworks

Self-assembly of individual units into multicomponent complexes is a powerful approach for the generation of functional superstructures. We present the coordinative interaction of oligohistidine-tags (His-tags) with metal–organic framework nanoparticles (MOF NPs). By this novel concept, different molecular units can be anchored on the outer surface of MOF NPs in a self-assembly process generating multifunctional nanosystems. The article focuses on two main objectives: first, the detailed investigation of the assembly process and fundamental establishment of the novel functionalization concept; and second, its subsequent use for the development of biomacromolecule (e.g., peptides and proteins) delivery vehicles. Three exemplary MOF structures, MIL-88A, HKUST-1, and Zr-<i>fum</i>, based on different metal components, were selected for the external binding of various His-tagged synthetic peptides and recombinant or chemically H<sub>6</sub>-modified proteins. Evidence for simultaneous assembly of different functional units with Zr-<i>fum</i> MOF NPs as well as their successful transport into living cells illustrate the promising potential of the self-assembly approach for the generation of multifunctional NPs and future biological applications. Taking the high number of possible MOF NPs and different functional units into account, the reported functionalization approach opens great flexibility for the targeted synthesis of multifunctional NPs for specific purposes.