UiO-66 metal-organic frameworks in biomedicine: From structural tunability to bioimaging, photodiagnostics, and photodynamic cancer therapy.

Abstract

UiO-66-type zirconium metal-organic frameworks (MOFs) have emerged as robust and highly tunable nanoplatforms for biomedical applications owing to their permanent porosity, exceptional chemical stability, and versatile functionalization pathways. Here, we summarize recent advances in engineering UiO-66-based nanoparticles for drug delivery, multimodal bioimaging, photodiagnostics, and photodynamic therapy (PDT). Precise control over composition, surface chemistry, and postsynthetic modifications allow for high drug loading, stimuli-responsive release, and improved colloidal stability in biological environments. Strategies for active targeting using antibodies, peptides, aptamers, and small-molecule ligands significantly enhance tumor specificity. Furthermore, UiO-66 is increasingly used as a carrier for photosensitizers, contrast agents, and imaging probes, supporting multimodal fluorescence, CT, MRI, and photoacoustic imaging. The framework's ability to coordinate photosensitizers and modulate oxygen availability provides powerful opportunities for PDT, especially in hypoxic tumors. However, key challenges remain, including long-term biocompatibility, clearance, and scalable synthesis. Future prospects include programmable degradation, advanced surface architectures, biomimetic coatings, and multimodal phototheranostic platforms.