Stimuli-responsive flexible metal-organic frameworks: a promising approach to drug delivery

Stimuli-responsive flexible metal-organic frameworks (MOFs), also known as "soft porous crystals" (SPCs). MOFs are the third generation of porous materials and have been getting more and more attention as potential candidates for smart drug delivery systems. The main characteristic of flexible MOF is the tunability of their structures and their dynamic responsiveness, which is a property not shared by traditional rigid MOF. Their frameworks are able to change upon a physical or chemical stimulus (such as pH, temperature and guest molecules), and thus they can achieve precise drug delivery and release. Although many reviews have addressed MOFs as drug delivery carriers, most of these reviews are either about strategies for drug loading or biomedical applications of MOFs, and to date none of these reviews have shed light on how the framework flexibility affects drug loading and stimuli-responsive drug release. In this review, the connection between structural dynamics of flexible MOFs and their pharmaceutical functions is explored, through its structural characteristics, synthetic strategies, response mechanisms and applications in anti-tumor therapy, bone regeneration as well as antibacterial treatment. In addition to the excellent property of enhancing drug load, this study also demonstrates that flexible MOFs can be used to realize the responsive drug release through their unique "breathing effect" and "gating effect". In addition, this study also provides an insight into flexible MOFs. This review suggests multi-stimulus responsive MOFs and integration of diagnosis and therapy platforms in MOFs and highlights the use of artificial intelligence (AI) technology to accurately predict the structure of flexible MOFs via structural design. Although more studies on safety, scalability, and clinical translation are still needed, these materials may have potential for future biomedical applications.