Design and Combinatorial Synthesis of Biomimetic Multivariate Metal-Organic Frameworks for Efficient Drug Loading

Multivariate metal-organic frameworks (MOFs) covering diverse iso-reticular materials while encompassing tunable function through the spatial composition of the organic functional groups are an excellent starting point for developing sequence-dependent materials. There remains a demand for synthesizing an extensive library of multivariate MOFs for function-targeted selection, similar to the process of directed evolution in improving the function of proteins by selecting the best mutant from a large mutant library. The design of biomimetic multivariate MOFs (bMTV-MOFs) is reported that incorporate the panel of functionality presented in amino acids to enable the complexity and adjustability of proteins to the structure of MOFs. A total of 1089 MOFs, ranging from single-component to multivariate structures, are synthesized in a combinatorial manner for the delivery of the verteporfin, a photosensitive drug. Tertiary bMTV-MOFs demonstrated superiority in the adsorption and release of verteporfin. In vitro studies on various cancer cell lines demonstrated a 23 to 68-fold enhancement in efficacy for photodynamic therapy using the privileged A₁F₆H₃ or A₃D₁H₆ bMTV-MOFs over pristine MOFs.