Folate-targeted Mg–alendronate BioMOF nanorods for pH-responsive drug release and selective cancer therapy

Abstract Herein, a bio-metal–organic framework (BioMOF) was synthesized using the bisphosphonate drug alendronate (ALD) as both the organic linker and therapeutic agent, coordinated with Mg²⁺ ions to form Mg–ALD. To enable active targeting, the framework was functionalized with folic acid (FA), yielding Mg–ALD/FA. The structural and morphological properties of the BioMOFs were characterized using scanning and transmission electron microscopy (SEM/TEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), Fourier-transform infrared spectroscopy (FTIR), and ultraviolet-visible (UV–Vis) spectroscopy. Drug release investigations revealed a pronounced pH-responsive behavior, with significantly enhanced ALD release under acidic conditions (pH 5.5) compared to physiological pH (7.4). Kinetic analysis suggested that the release process is predominantly diffusion-controlled under physiological conditions, while weakening of Mg–ALD coordination under acidic environments. In vitro cytotoxicity studies (MTT assay) on NIH/3T3, HeLa, and LnCap cell lines demonstrated selective toxicity of Mg–ALD/FA toward folate receptor–positive HeLa cells, while minimal effects were observed on normal and FA-negative cells. After 72 h of treatment with 50 µg mL⁻¹ Mg–ALD/FA, HeLa cell viability decreased to approximately 25%. These findings demonstrate that Mg–ALD/FA represents a dual-function BioMOF in which alendronate serves simultaneously as a structural linker and therapeutic agent, offering controlled pH-responsive release and effective receptor-mediated targeting for cancer therapy.