Recent Advances in Supramolecular Systems for Precision Medicine: Structural Design, Functional Integration, and Clinical Translation Challenges.

Non-covalent and dynamic covalent interactions enable supramolecular systems to function as adaptive platforms in biomedical research, offering novel strategies for precision medicine applications. This review examines five-year developments in supramolecular applications across precision medical domains, including disease diagnosis, bioimaging, targeted drug delivery, tissue engineering, and gene therapy. The review begins by systematically categorizing supramolecular structures into dynamic covalent systems (e.g., disulfide bonds, boronate esters, and hydrazone bonds) and dynamic non-covalent systems (e.g., host-guest interactions, hydrogen-bond networks, metal coordination, and π-π stacking), highlighting current strategies employed to optimize their responsiveness, stability, and targeting efficiency. Representative case studies, such as cyclodextrin-based nanocarriers and metal-organic frameworks (MOFs), are thoroughly analyzed to illustrate how supramolecular systems can enhance precision in drug delivery and improve biocompatibility. Furthermore, this article critically discusses major challenges faced during clinical translation, encompassing structural instability, inadequate specificity of environmental responsiveness, pharmacokinetic and toxicity concerns, and difficulties in scalable manufacturing. Potential future directions to overcome these barriers are proposed, emphasizing biomimetic interface engineering and dynamic crosslinking strategies. Collectively, the continued evolution in structural optimization and functional integration within supramolecular systems holds great promise for achieving personalized diagnostic and therapeutic platforms, thereby accelerating their translation into clinical practice and profoundly shaping the future landscape of precision medicine.