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

Abstract

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 (<b>TDL-Mg</b>), was constructed by employing π-conjugated 1,3,6,8-tetrakis(<i>p</i>-benzoic acid)pyrene (<b>H</b>_<b>4</b><b>TBAPy</b>) as a ligand and used for 5-fluorouracil (5-FU) loading (28.2 wt %) and sustained slow release. <b>TDL-Mg</b> exhibits a 3D supramolecular architecture featuring a 1D rectangle channel with a size of 6.2 × 8.1 Ų and a Brunauer-Emmett-Teller surface area of 627 m²·g^-1. Channel microenvironment analysis shows that the rigid <b>H</b>_<b>2</b><b>TBAPy</b>^<b>2-</b> 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@<b>TDL-Mg</b> 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@<b>TDL-Mg</b> 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.