Advances in metal-organic frameworks (MOFs) for nanotheranostics: from targeted drug delivery to multimodal imaging.

The integration of diagnostic and therapy into a single nanoplatform has been proved to be a revolutionary approach for precision medicine, which allows the simultaneous disease detection, treatment, and therapeutic monitoring. Although great progress has been achieved in nanotheranostics, many traditional nanomaterials still suffer from low drug loading capacity (LC), inefficient targeting, insufficient reactivity to the complex tumor microenvironment (TME), and limited integration of diagnostic and therapeutic functions. These issues have led to increased interest in metal-organic frameworks (MOFs), a flexible family of crystalline porous materials built from metal ions or clusters bridged by organic ligands. The ultra-high surface area, customizable pore architecture, programmable composition, structural diversity, and simple surface functionalization have made MOFs interesting candidates for next-generation nanotheranostic systems. MOFs have emerged as adaptable platforms for the concurrent administration of therapeutic drugs and imaging probes, enabling integrated theranostic applications, as evidenced by recent advancements. Moreover, the integration of stimuli-responsive drug release, TME-activated catalytic therapeutic mechanisms, and multimodal imaging modalities such as magnetic resonance imaging (MRI), computed tomography (CT), fluorescence imaging (FL), photoacoustic imaging (PAI), and positron emission tomography (PET) has significantly broadened the scope of MOF-mediated precision diagnosis and therapy. In addition to conventional drug delivery, novel MOF nanoplatforms have been designed to induce ferroptosis, chemodynamic therapy, phototherapy (PT), immunomodulation, and other synergistic therapeutic methods, thus improving therapeutic efficacy with minimized off-target harm. This review highlights the recent advances in MOF nanotheranostics covering design strategies, targeted drug delivery, imaging and multifunctional therapeutic applications. The challenges of biosafety, biodegradation, pharmacokinetics, large-scale manufacturing and clinical translation are critically discussed.