Synthetic and biological identities of layered double hydroxides nanocarriers functionalized with risedronate

Abstract Layered double hydroxide nanoparticles (LDH-NP) provide new therapeutic opportunities to improve drug distribution, stability, and effectivity. Nevertheless, these LDH-NP present a different behavior in biological medium due to their interaction with biomolecules (biological identity) to that of as-synthesized LDH-NP (synthetic identity). In this work, both identities were compared for LDH-NP functionalized with risedronate. First, physical interactions between as-synthesized LDH-NP and the cell membrane were studied using giant unilamellar vesicles (GUVs). Then, their biological identity was formed in bovine fetal serum and explored with a proteomic approach and the mapping of protein-protein interactions. Finally, the effect of functionalization and biological identity on drug delivery capacity was tested in methotrexate loaded LDH-NP. As a result of their opposite zeta potential, bare LDH-NP (ζ > +40 mV) increased the permeability of the negatively charged GUVs, while Ris functionalized LDH-NP (ζ