Metal-organic frameworks as therapeutic chameleons: revolutionizing the cancer therapy employing novel nanoarchitectonics

Cancer is one of the most complex diseases and the second leading cause of mortality worldwide. Due to its poor prognosis and challenges in diagnosis, eradicating cancer remains highly difficult. The limitations associated with conventional therapies have led to the emergence of copious therapeutic strategies such as chemotherapy, phototherapy, starvation therapy, radiotherapy and immunotherapy; however, limited therapeutic efficacy, poor tumor cell selectivity and substantial adverse effects remain significant concern. Attributed to the expeditious advancement of nanotechnology, the amalgamation of nanomaterials with therapeutic approaches provides an opportunity to address the shortcomings of conventional chemotherapy. Metal-organic frameworks (MOFs), which consist of bridging ligands and ions/clusters connected by coordination bonds, have been widely used in cancer therapy to address the limitations of currently therapeutic interventions, such as poor efficacy, low stability and severe side effects. This potential arises from their tuneable porosities, high specific surface area-to-volume ratio, tailorable diameters, tractable morphologies, variegated compositions, biocompatibility and facile functionalization. We summarized the role of MOF-based nanoplatforms along with mechanistic insights into emerging avenues-such as cuproptosis, ferroptosis, cell-penetrating and biomimetic MOFs, and tumor microenvironment-responsive MOFs- alongside recent advancements in mono- and multifunctional cancer therapeutics. Theragnostic and imaging functionalities, as well as regulatory considerations and future prospects of MOF-based nanoplatforms utilized in cancer treatment, are also discussed.