Targeting, Tracking, and Triggering: Versatile Applications of Zr-MOFs in Drug Delivery, Theranostic Platforms, and Advanced Biosensing

Zirconium-based metal-organic frameworks (Zr-MOFs) have emerged as promising platforms for biomedical analysis owing to the exceptional chemical and hydrolytic stability imparted by their robust Zr6 secondary building units (SBUs). Strong Zr-O coordination bonds and high framework connectivity enable these materials to retain structural integrity under physiological conditions, overcoming limitations of conventional systems such as instability, leaching, and nonspecific interactions. This review critically explores the applications of Zr-MOFs in three interconnected areas: stimuli-responsive drug delivery with integrated analytical monitoring, multimodal bioimaging (PET, CT, and near-infrared fluorescence) for real-time diagnostics, and advanced biosensing, with emphasis on electrochemiluminescence, fluorescence, and nanozyme-based detection of clinically relevant biomarkers. Organized around the concepts of Targeting, Tracking, and Triggering, the review highlights how the intrinsic stability of Zr6 SBUs, combined with defect engineering, surface functionalization, stimuli-responsive gating, and self-calibrating strategies, enhances analytical performance. Beyond summarizing applications, it critically compares design approaches, evaluates key performance metrics, including drug loading, detection limits, matrix tolerance, and in vivo stability, and discusses major translational challenges such as scalable synthesis, real-sample validation, and long-term biocompatibility. Finally, emerging opportunities in AI-assisted inverse design and green manufacturing are highlighted to accelerate the clinical translation of Zr-MOFs.