CONICET | Buscador de Institutos y Recursos Humanos

Layered double hydroxides nanoparticles (LDH-NPs) present excellent properties to grant the complexfunctionality needed for biomedical applications. They can be easily prepared with a size between 50 and 200nm and their anion exchange capacity provides a high loading capacity for acid drugs and biomolecules. Besides,they present release mechanisms based on the anion exchange with the anions in the biological media and thedissolution of their layers at slightly acid media [1]. Nevertheless, there are many aspects regarding thephysicochemical properties of LDH-NPs and their interaction with the biological media that are still unclear torationally design LDH-NPs with genuine potential to be applied in biomedical applications.A precise control of the LDH-NPs size is necessary to ensure their capacity to evade clearing by themononuclear phagocyte system (MPS) and to optimize the transfection capacity of the cellular membrane [2].Likewise, new strategies to surface functionalize LDH-NPs are required to increase their colloidal stability inbiological media, and to provide site specificity. Another aspect to be addressed is the interaction between serumproteins and the surface of LDH-NPs that produces a biological coating known as protein corona. The proteincorona determines the physicochemical properties of LDH-NPs and their interactions with the cellularmembrane, which leads to a so-called ?biological identity? that can be quite different to that of the as-preparedLDH-NPs. Controlling the biological identity of LDH-NPs is a key aspect to reduce elimination by the MPS andto optimize the interaction with the target cells.Here we present diverse strategies to control the physicochemical properties and biological interactions of LDHNPs.In first place, different synthesis routes were explored to intercalate anions such as methotrexate,fluorescein or nalixidate, the best results being obtained with a coprecipitation method at variable pH involvingseparate nucleation and aging steps [3]. Secondly, different compounds were used to functionalize thesynthesized LDH-NPs: risedronate, a bone antiresorptive drug with high affinity for hydroxyapatite, was used toprovide bone targeting capabilities, while polylelectrolytes were explored to enhance their colloidal stability.Finally, the interaction between albumin and LDH-NPs was studied as a first insight to the protein coronaformation mechanism and its effect on the physicochemical properties of LDH-NPs. Afterwards, the biologicalidentity of LDH-NPs and its modulation by the surface coating with serum proteins was explored in cell cultureconditions. The cytotoxicity and transfection capacity of the prepared LDH-NPs were tested in adequate modelcell lines.The use of different synthetic strategies and a careful selection of the operational parameters allowed thesynthesis of LDH-NPs with different interlayer anions. In all cases, the drug was selectively located in theinterlayer of the LDH-NPs, which allowed their surface functionalization with a minor drug loss. Thefunctionalization with either risedronate and polyacrylate increased the colloidal stability of LDH-NPs even inhigh ionic strength due to electrostatic repulsion and/or steric impediments. Further, risedronate functionalizedLDH-NPs attached to hydroxyapatite due to risedronate bridging. A protein corona was formed on the LDH-NPssurface in all cases upon interaction with serum proteins; albumin was its main component in all cases. Theextent of the protein adsorption, as well as the components of the protein corona were affected byfunctionalization, which ultimately affected the unspecific cell transfection of LDH-NPs. These studies clearlyshow the potential of rationally and thoroughly designed LDH-NPs to produce drug delivery to specific tissuesand cells.