Pomegranate and Cherry Leaf Extracts as Stabilizers of Magnetic Hydroxyapatite Nanocarriers for Nucleic Acid Delivery

Small interfering RNAs (siRNAs) provide strong therapeutic potential due to their efficient gene-silencing properties; however, their instability limits clinical application. Nanoparticle carriers may overcome this problem; in particular, magnetic nanoparticles show great promise as they can be directed to the target sites by external magnetic fields, thus improving delivery efficiency and reducing off-target effects. In addition, magnetic nanoparticles offer a novel nanoplatform for theranostic applications, integrating siRNA delivery with magnetic resonance imaging and magnetic hyperthermia for synergistic diagnostic and therapeutic advantages. The present work reports the development of a novel platform based on biomimetic magnetic nanoparticles made of Fe(II)/Fe(III)-doped apatite (FeHA) nucleated and grown in the presence of cherry and pomegranate leaf extracts to enhance the colloidal stability and make it suitable for nucleic acid delivery under the guidance of magnetic fields. This approach allowed the obtention of FeHA suspension with increased negative zeta potential leading to very good stability. In addition, the functionalization with natural extracts conferred antioxidant properties also favoring the maintenance of the Fe(III)/Fe(II) ratio in the apatitic structure, inducing the superparamagnetic properties. To evaluate the delivery capability of the system, a model GAPDH-targeting siRNA molecule was employed. Its interaction with the nanoplatform was characterized by assessing loading capacity and release kinetics, which were further interpreted using mathematical modeling to elucidate the underlying release mechanisms.