One-Pot Synthesis of Bioinspired Peptide-Decorated Apatite Nanoparticles for Nanomedicine

Mathilde Guérin, Aurélien Lebrun, Liisa Kuhn, Thierry Azaïs, Guillaume Laurent, Olivier Marsan, Christophe Drouet, and Gilles Subra


Hybrid organic-inorganic bio-inspired apatite nanoparticles (NPs) are attractive for biomedical applications and especially in nanomedicine. Unfortunately, functionalized apatite NPs were so far synthesized by multistep processes and often yielding broad particle size distributions. In addition, although the adsorption of drugs or antibodies on apatite NPs surfaces was reported, it was generally associated with uncontrolled drug loading. All these limitations have restricted their actual applications in nanomedicine. Besides, very few attempts at exposing bioactive peptides on apatite NPs have been made. In this work, we report an original one-pot synthesis of well-defined bioactive hybrid NPs composed of a mineral core of bioinspired apatite surrounded by an organic corona of bioactive peptides. Dual stabilizing-bioactive agents, phosphonated PEG-peptide conjugates, were prepared and directly used during apatite precipitation (i) to form the organic corona during apatite precipitation, driving the size and shape of resulting hybrid NPs with colloidal stabilization and (ii) to expose peptide moieties (RGD or YIGSR sequences) at the NPs periphery in view of conferring additional surface properties to enhance their interaction with cells. Here, we demonstrate the success of this approach, we fully characterized the functionalized NPs by FTIR, Raman, XRD, solid and liquid state NMR, TEM and DLS, and we followed their interaction with fibroblast cells, unveiling a synergistic proliferative effect.