A closer look into the physical interactions between lipid membranes and layered double hydroxide nanoparticles

Layered double hydroxide nanoparticles (LDH-NPs) constitute promising nanocarriers for drug and gene delivery. Although their cell internalization has been studied, the interaction between LDH-NPs and biological membrane models, such as giant unilamellar vesicles (GUVs), remains unexplored. These vesicles are widely-used membrane models that allow minimizing the complexity and uncertainty associated with biological systems to study the physical interactions in the absence of cell metabolism effects. With such an approach the physicochemical properties of the membrane can be differentiated from the biological functionalities involved in cell internalization and the membrane-mediated internalization can be directly understood. In this work, we describe for the first time the interaction of LDH-NPs with freestanding negatively charged POPC:POPS GUVs by fluorescence microscopy. The experiments were performed with fluorescein labeled LDH-NPs of about 100 nm together with different fluorophores in order to evaluate the NPs interactions with the vesicles as well as their impact on the membrane morphology and permeability. Positively charged LDH-NPs are electrostatically accumulated at the GUVs membrane, altering its lateral phospholipid distribution and increasing the stiffness and permeability of the membrane. The adsorption of albumin (LDH@ALB) or polyacrylic acid (LDH@PA) passivates the surface of LDH-NPs eliminating long-range electrostatic attraction. The absence of membrane-mediated internalization of either LDH@ALB or LDH@PA, represents an advantage in the use of LDH-NPs as drug or nucleic acids nanocarriers, because suitable functionalization will allow an optimal cell targeting.