A Luminescent Mg-Metal–Organic Framework for Sustained Release of 5‑Fluorouracil: Appropriate Host–Guest Interaction and Satisfied Acid–Base Resistance

It
is important to achieve a moderate sustained release rate for drug
delivery, so it is critical to regulate the host–guest interactions
for the rational design of a carrier. In this work, a nano-sized biocompatible
metal–organic framework (MOF), Mg­(H2TBAPy)­(H2O)3·C4H8O2 (TDL-Mg), was constructed by employing π-conjugated
1,3,6,8-tetrakis­(p-benzoic acid)­pyrene (H4TBAPy) as a ligand and used
for 5-fluorouracil (5-FU) loading (28.2 wt %) and sustained slow release. TDL-Mg exhibits a 3D supramolecular architecture featuring
a 1D rectangle channel with a size of 6.2 × 8.1 Å2 and a Brunauer–Emmett–Teller surface area of 627 m2·g–1. Channel microenvironment analysis
shows that the rigid H2TBAPy2– ligand adopts special
torsion to stabilize the channels and offer rich π-binding sites;
the partially deprotonated carboxyls not only participate in the formation
of strong hydrogen bonds but also create a mild pH buffer environment
for biological applications. Suitable host–guest interactions
are generated by the synergistic effect of polydirectional hydrogen
bonds, multiple π-interactions, and confined channels, which
allow 5-FU@TDL-Mg to release 76% of load in 72 h, a medically
reasonable rate. Microcalorimetry was used to directly quantify these
host–guest interactions with a moderate enthalpy of 22.3 kJ·mol–1, which provides a distinctive thermodynamic interpretation
for understanding the relationship between the MOF design and the
drug release rate. Additionally, the nano-sized 5-FU@TDL-Mg can be taken up by mouse breast cancer cells (4T1 cells) for imaging
based on the dramatic fluorescence change during the release of 5-FU,
exhibiting potential applications in biological systems.

药物递送领域实现适度持续释药速率至关重要，因此合理调控主客体相互作用（host–guest interactions）以理性设计药物载体是核心关键。本研究以π共轭的1,3,6,8-四(对苯甲酸)芘（H4TBAPy）为配体，构建了一种纳米级生物相容性金属有机框架（metal–organic framework, MOF）材料Mg(H2TBAPy)(H2O)3·C4H8O2（命名为TDL-Mg），并将其用于负载5-氟尿嘧啶（5-fluorouracil, 5-FU），负载量可达28.2 wt%，且可实现持续缓释。TDL-Mg呈现三维超分子结构，拥有尺寸为6.2 × 8.1 Ų的一维矩形孔道，其布鲁诺尔-埃梅特-特勒（Brunauer–Emmett–Teller, BET）比表面积达627 m²·g⁻¹。孔道微环境分析表明，刚性的H2TBAPy²⁻配体通过特殊的扭转构象稳定孔道，并提供丰富的π结合位点；部分去质子化的羧基不仅参与形成强氢键作用，还可为生物应用构建温和的pH缓冲环境。通过多方向氢键、多重π相互作用与限域孔道的协同效应，体系形成了适宜的主客体相互作用，使得5-FU@TDL-Mg在72小时内可释放76%的负载药物，释药速率符合医学合理范围。研究采用微量热法（microcalorimetry）直接定量表征该主客体相互作用，测得其焓变为22.3 kJ·mol⁻¹，为理解MOF设计与药物释放速率之间的关联提供了独特的热力学解释。此外，该纳米级5-FU@TDL-Mg可被小鼠乳腺癌细胞（4T1细胞）摄取，并基于5-FU释放过程中的显著荧光变化实现成像，展现出在生物系统中的应用潜力。