New insights about the intercalation of 5-Fluorouracil into 2D Mg–Al layered double hydroxide nanosheets: A theoretical and experimental investigation

Abstract

Layered double hydroxides (LDH) are interesting 2D inorganic platforms for biomedical purposes. In contrast to previous studies, this work reports the intercalation of 5-Fluorouracil (5-FU) into LDH through anion exchange using a fresh LDH material without the need for any organic compound or treatment prior to the intercalation with 5-FU. The combination of experimental charaterizations and computational studies allowed us to study the intercalation process, where the presence of three phases in the hybrid material are suggested: two of them are related to different charge states of the intercalated 5-FU into 2D LDH interlayer space, and the third one might be related to some kind of distorted LDH. FTIR, XPS and DFT calculations indicated that interactions established in the host-guest system involve a complex network of hydrogen bonds, contributing to the improvement of the chemical and thermal stability of the 5-FU-LDH hybrid. Release assays of 5-FU from the 5-FU-LDH demonstrated the ability to selectively release the drug in simulated tumor microenvironment, while in vitro bioassays suggested a dose-dependent behavior of the hybrid. These results contribute to a better understanding of the chemistry of intercalation of 5-FU into 2D-LDH, and can be used to tune properties of 5-FU-LDH in antitumor therapy.