Ma Xiaomin, Xiao Yazhe, Li Shuyu, Du Jianghai, Wang Junjie, Peng Xingzhou
State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Sanya 572025, China.
NHC Key Laboratory of Tropical Disease Control, School of Life Science and Medical Technology, Hainan Medical University, Haikou 571199, China.
Pharmaceutics. 2025 Sep 13;17(9):1192. doi: 10.3390/pharmaceutics17091192.
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.
非共价和动态共价相互作用使超分子系统能够作为生物医学研究中的适应性平台发挥作用，为精准医学应用提供了新策略。本综述考察了超分子在精准医疗领域应用的五年发展情况，包括疾病诊断、生物成像、靶向给药、组织工程和基因治疗。综述首先将超分子结构系统地分类为动态共价系统（如二硫键、硼酸酯和腙键）和动态非共价系统（如主客体相互作用、氢键网络、金属配位和π-π堆积），强调了目前用于优化其响应性、稳定性和靶向效率的策略。对基于环糊精的纳米载体和金属有机框架（MOF）等代表性案例进行了深入分析，以说明超分子系统如何提高药物递送的精准性并改善生物相容性。此外，本文批判性地讨论了临床转化过程中面临的主要挑战，包括结构不稳定性、环境响应特异性不足、药代动力学和毒性问题以及规模化制造困难。提出了克服这些障碍的潜在未来方向，强调了仿生界面工程和动态交联策略。总体而言，超分子系统在结构优化和功能整合方面的持续发展有望实现个性化诊断和治疗平台，从而加速其向临床实践的转化，并深刻塑造精准医学的未来格局。
