Impact of nucleic acid encapsulated MOF crystal phase on protein corona formation

Abstract

Metal-organic frameworks (MOFs) are among the most extensively studied materials for delivering a wide range of therapeutic entities including proteins, carbohydrates, and nucleic acids. Despite significant efforts, the effect of serum proteins on MOFs is still not well understood. The biological identity and fate of therapeutic biocomposites are altered in a biological environment due to the formation of a protein corona around nanomaterials. Although the crystalline property of MOFs controls their biological interactions, the influence of these properties on the MOF-protein interaction is not well understood. Herein, we study the mechanism of interaction of a nucleic acid-encapsulated Zn-based zeolitic imidazolate framework-8 (ZIF-8) and its carbonate-rich variant (ZIF-C) with human serum albumin (HSA). It is found that different crystal topologies of these ZIFs affect their interaction with serum albumin. The key finding is that ZIF-8 has the tendency to interact more strongly with serum proteins compared to ZIF-C. Considering that ZIF-8 tends to spontaneously transform into ZIF-C in an aqueous environment, these findings may have important implications in the rationale design of MOF-based therapeutic agents.