Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710127, China.
Shaanxi Key Laboratory of Comprehensive Utilization of Tailings Resources, College of Chemical Engineering and Modern Materials, Shangluo University, Shangluo 726000, China.
ACS Appl Mater Interfaces. 2020 Apr 1;12(13):14914-14923. doi: 10.1021/acsami.0c01198. Epub 2020 Mar 21.
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(HTBAPy)(HO)·CHO (), was constructed by employing π-conjugated 1,3,6,8-tetrakis(-benzoic acid)pyrene () as a ligand and used for 5-fluorouracil (5-FU) loading (28.2 wt %) and sustained slow release. exhibits a 3D supramolecular architecture featuring a 1D rectangle channel with a size of 6.2 × 8.1 Å and a Brunauer-Emmett-Teller surface area of 627 m·g. Channel microenvironment analysis shows that the rigid 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@ 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, 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@ 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.
实现药物输送的适度持续释放速率很重要，因此调节主体-客体相互作用对于载体的合理设计至关重要。在这项工作中，构建了一种纳米尺寸的生物相容性金属有机骨架（MOF），Mg(HTBAPy)(HO)·CHO ()，采用π-共轭 1,3,6,8-四（-苯甲酸）芘（）作为配体，用于负载（28.2wt%）和持续缓慢释放 5-氟尿嘧啶（5-FU）。表现出 3D 超分子架构，具有 6.2×8.1Å的 1D 矩形通道和 627 m·g 的 Brunauer-Emmett-Teller 表面积。通道微观环境分析表明，刚性配体采用特殊扭曲来稳定通道并提供丰富的π结合位点；部分去质子化的羧基不仅参与形成强氢键，而且为生物应用创造温和的 pH 缓冲环境。通过多方向氢键、多π相互作用和受限通道的协同作用产生合适的主体-客体相互作用，允许 5-FU@在 72 小时内释放 76%的负载，这是一个合理的医学速率。微量热法直接定量这些主体-客体相互作用，其焓值适中，为 22.3 kJ·mol，为理解 MOF 设计与药物释放速率之间的关系提供了独特的热力学解释。此外，纳米尺寸的 5-FU@可以被小鼠乳腺癌细胞（4T1 细胞）摄取，用于基于 5-FU 释放过程中荧光剧烈变化的成像，显示出在生物系统中的潜在应用。
