Metal- and covalent-organic framework-based drug delivery systems: Applications to control cell functions

Tissue engineering and regenerative medicine are interdisciplinary fields that aim to repair structural or functional defects in target tissues by replicating the physiological characteristics and microenvironments of organs. Despite advancements in nanotechnology and biomimetics, effectively controlling cell functions remains challenging due to discrepancies between in vitro and in vivo cellular microenvironments. The extracellular microenvironment provides physical and chemical cues influencing cellular functions such as migration, proliferation, differentiation, and apoptosis. In response, various drug delivery systems (DDSs) have been developed to modulate cell fate by delivering chemical cues that influence or integrate cellular signalling pathways. However, conventional drug delivery methods often suffer from limitations such as low stability and poor cellular uptake. To address these issues, DDSs based on porous nanomaterials, including metal-organic frameworks (MOFs) and covalent-organic frameworks (COFs), have been introduced. These materials offer well-defined pore structures and extensive surface area, increasing drug-loading capacity and facilitating sustainable release of various physicochemical substances through their tunable properties. Additionally, they exhibit catalytic activity that enables precise control of drug release in response to external conditions such as light, temperature, and pH. MOFs and COFs can be used alone or combined with other nanomaterials to achieve synergistic effects. This review discusses recent MOF- and COF-based DDS advancements for controlling cell functions and highlights strategies for enhancing drug delivery efficiency and tissue penetration.