Enhancing cellular uptake and cytosolic delivery of Nano MOFs: Synthesis approaches and strategies to overcome clearance

Metal-organic frameworks (MOFs) have become a highly promising platform for drug delivery systems, thanks to their unique and advantageous properties. These include exceptional thermal, chemical, and water stability, biocompatibility (when specific metals and ligands are selected), high porosity due to their cluster and ligand structure, and extremely large surface areas. Together, these features make MOFs exceptionally well-suited for adsorbing and delivering a wide range of drugs, as evidenced by this extensive research. By carefully choosing metals and ligands, along with controlling reaction conditions such as reaction time, temperature, solvent type, pH media, reactant molar ratios and the use of modulators, researchers can precisely design the shape, size, and overall structure of MOF particles. This review thoroughly examines the specific methods used in these processes. It covers various synthesis techniques, including hydrothermal, solvothermal, reflux, sonochemistry, microwave, electrochemical, and mechanochemical approaches. Additionally, the review explores the materials and strategies essential for ensuring the biocompatibility and effective biomedical use of nMOFs. Special attention is placed on the size, shape, and final morphology, including surface characteristics of MOF particles, as these parameters critically influence their cellular interactions and uptake efficiency. These physicochemical properties are crucial because they directly influence how effectively the nanoparticles can move through biological barriers and reach their intended intracellular targets without breaking down or losing their structural integrity.