Topology-engineered radio-theranostic layered double hydroxide nanocarrier via surface modification with spacer-linked cancer targeting ligand and lattice-integrated radioisotope

Abstract

A theranostic hybrid nanomaterial was synthesized by incorporating functional moieties such as anticancer drug methotrexate (MTX), cancer targeting ligand folic acid (FA) and a radioisotope, Co-57, into topological sites of layered double hydroxide (LDH). The surface of the drug intercalated LDH (MTX-LDH) was successfully modified with FA utilizing hexamethylene diamine (HDA) as a spacer. The radioisotope, Co-57, was then incorporated into the frameworks of the surface-modified LDH (Co@FHML) via a hydrothermal method in order to preserve the crystalline phase and particle size of the LDH during the incorporation. The incorporated Co-57 was found to be stably retained for more than five days under human serum conditions, indicating the stable lattice inclusion of the radioisotope. The hydrophilic property of the LDH was preserved even after the surface modification with organic moieties, ensuring dispersibility and stability in physiological media. Cell internalization results and the microscopic images of the folate receptor (FR) over-expressing CT-26 and MDA-MB-231 cancer cells demonstrated the successful delivery of MTX into the tumor cells by Co@FHML. © 2025 Elsevier B.V.