Controlled Zn2+-Triggered Drug Release by Preferred Coordination of Open Active Sites within Functionalization Indium Metal Organic Frameworks

Drug delivery in target regions could make extraordinary progress in chemoselective therapies. A novel preferred coordination (PC) strategy referring to proactive interacting with open active sites to replace previous occupation by ion-exchange for controlling release of drug molecules is well-constructed. Two topological types of MOF-In1 (Schläfli symbol: (4,8)-connected of (410·615·83)­(45·6)2) and MOF-In2 (Schläfli symbol: (4,4)-connected of (66)) show the specific way. Increasing node connectivity as well as the trapping of guest OH– anions, 5-fluorouracil (5-FU) is preferentially captured into the MOF-In1, which exhibits an outstanding loading capacity around 34.32 wt %. 19F NMR spectroscopy was further employed to investigate host–guest interaction and reveal the binding constant (Ka = 3.84 × 102 M–1). Meanwhile, the controlled release of 5-FU in a simulated human body with liquid phosphate-buffered saline solution by biofriendly Zn2+-triggered is realized. With an elevated Zn2+ concentration, the drug release will be enhanced. This efficient strategy for MOFs as multifunctional drug carrier opens a new avenue for biological and medical applications.

靶向区域给药有望在化学选择性治疗领域取得突破性进展。本研究构建了一种新型优先配位（Preferred Coordination, PC）策略：通过主动与开放活性位点结合，替代此前依赖离子交换的占位方式，实现药物分子释放的精准调控。两种拓扑结构的铟基金属有机框架（Metal-Organic Framework, MOF）-In1（施莱夫利符号（Schläfli symbol）：(4,8)-连接型，拓扑式为(4¹⁰·6¹⁵·8³)(4⁵·6)₂）与MOF-In2（施莱夫利符号：(4,4)-连接型，拓扑式为(6⁶)）展示了该策略的具体实现路径。通过提升节点连通性并捕获客体OH⁻阴离子，5-氟尿嘧啶（5-fluorouracil, 5-FU）可优先被吸附至MOF-In1中，该材料的载药量可达34.32 wt%，性能优异。后续通过¹⁹F核磁共振（Nuclear Magnetic Resonance, NMR）光谱表征了主客体相互作用，并测得其结合常数Ka=3.84×10² M⁻¹。同时，本研究在模拟人体环境的磷酸盐缓冲生理盐水体系中，实现了生物友好型Zn²⁺触发的5-FU可控释放；且随着Zn²⁺浓度升高，药物释放速率会相应提升。该将金属有机框架用作多功能药物载体的高效策略，为生物医学领域的应用开辟了全新路径。