Noncovalent Interaction‐Mediated Metal‐Organic Framework‐Based Theranostic Systems for Precision Medicine

Comprehensive Summary Theranostics combines diagnostic and therapeutic functions to enable personalized treatment strategies in precision medicine. Metal‐organic frameworks (MOFs) have emerged as promising platforms for such applications due to their tunable porosity and multifunctionality. Noncovalent interactions, including hydrogen bonding, π–π stacking, electrostatic forces, and hydrophobic effects, play crucial roles in governing drug loading, stimuli‐responsive release, and structural stability of these systems. This review examines the mechanistic contributions of noncovalent interactions in MOF‐based theranostics and explores how machine learning approaches can facilitate rational design through systematic analysis of interaction patterns. We survey recent applications in treating cancer, infectious diseases, cardiovascular disorders, and metabolic conditions. Current challenges and future opportunities are discussed, including artificial intelligence (AI)‐assisted design strategies, integration of multimodal theranostic functions, and pathways toward clinical implementation. Key Scientists Since Yaghi's pioneering work on metal‐organic frameworks (MOFs) in 1995, the field of diagnostics and therapeutics has undergone a revolutionary transformation. [1‐2] The unique porous architecture, tunable framework composition, and abundant noncovalent interaction sites of MOFs provide an ideal platform for drug loading, controlled release, and biomolecular recognition, with these noncovalent interactions integral to MOF‐based theranostic systems. In drug delivery, Férey and Serre made seminal contributions: demonstrating efficient ibuprofen loading in MIL‐series MOFs in 2006, [3] developing flexible MIL‐53 for controlled release in 2008, [4] and applying iron‐based MOFs for anticancer and antiviral delivery in 2010. [5] Concurrently, Lin pioneered nanoMOF‐based magnetic resonance imaging in 2006 [6] and achieved synergistic photodynamic therapy with immune checkpoint blockade inducing abscopal tumor regression in 2016, [7] establishing a comprehensive MOF nanomedicine paradigm. Fairen‐Jimenez developed systematic frameworks encompassing computational screening, surface engineering, and cellular mechanisms. [8‐10] In 2015, our group first introduced supramolecular gating approaches on MOF surfaces for precision drug release. [11] Liu innovatively integrated Tang's aggregation‐induced emission (AIE) concept [12‐13] into MOF systems for fluorescence imaging. [14] Recently, Zhang developed gadolinium‐based MOFs exhibiting bioorthogonal radiosensitization for bacterial theranostics and radiotherapy. [15‐16] Collectively, these advances have established MOFs as a powerful platform bridging molecular design with precision medicine.