Metal-organic frameworks for cancer drug delivery: Molecular design, therapeutic mechanisms, safety, and clinical translation

Metal-organic frameworks (MOFs) are tuneable porous platforms for cancer drug delivery, as their metal nodes, organic linkers, pore architecture, and surface chemistry can be engineered to control cargo loading, targeting, degradation, and stimulus-responsive release. This review critically discusses the composition-structure-function relationships that govern the performance of MOF-based cancer nanomedicines, focusing on drug encapsulation, tumour-targeted delivery, endogenous and externally triggered release, multimodal therapy and theranostics applications. Much attention has been paid to the effect of MOF composition on the stability of the framework, biodegradation, interactions between drugs and frameworks, therapeutic efficacy and biosafety. The review also addresses MOF-triggered cancer-cell-death mechanisms including apoptosis, ferroptosis, immunogenic cell death, autophagy-related responses, metabolic/starvation-induced death and novel cuproptosis-based approaches. Altogether, the current evidence suggests that MOFs can not only serve as passive drug carriers but also as compositionally programmable therapeutic platforms capable of modulating the tumour microenvironment and triggering complementary anticancer mechanisms. However, the clinical translation of such systems is hampered by framework-dependent toxicity, incomplete knowledge of long-term degradation and clearance, biological and manufacturing variability, scale-up challenges, and limited clinical validation. Compared to reviews that focus on specific families of MOFs or treatment modalities, this review combines composition-dependent performance, drug-delivery mechanisms, cancer-cell-death pathways, biosafety, translational barriers, and comparative nanomedicine considerations under a single framework. This integrated perspective highlights the need to move MOF development from increasingly complex preclinical constructs to reproducible, safety-oriented, and clinically translatable nanomedicines.

Abstract from PubMed (PMID 42966052). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.