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

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 < −40 mV) showed a much lower permeability increase. Also, a heavily interconnected protein corona with more than 70 different proteins was formed on bare LDH-NP while the number and interconnection of the proteins in the corona were diminished on Ris functionalized ones. Also, Ris functionalization only slightly diminished the drug loading capacity of the nanocarriers, which nevertheless showed a significant cytotoxic effect associated to the intercalated drug.