Pre-adsorption of antibodies enables targeting of nanocarriers despite a biomolecular corona

Manuel Tonigold, Johanna Simon, Diego Estupiñán, Maria Kokkinopoulou, Jonas Reinholz, Ulrike Kintzel, Anke Kaltbeitzel, Patricia Renz, Matthias P. Domogalla, Kerstin Steinbrink, Ingo Lieberwirth, Daniel Crespy, Katharina Landfester, Volker Mailänder

To promote drug delivery to exact sites and cell types, the surface of nanocarriers is functionalized with targeting antibodies or ligands, typically coupled by covalent chemistry. Once the nanocarrier is exposed to biological fluid such as plasma, however, its surface is inevitably covered with various biomolecules forming the protein corona, which masks the targeting ability of the nanoparticle. Here, we show that we can use a pre-adsorption process to attach targeting antibodies to the surface of the nanocarrier. Pre-adsorbed antibodies remain functional and are not completely exchanged or covered by the biomolecular corona, whereas coupled antibodies are more affected by this shielding. We conclude that pre-adsorption is potentially a versatile, efficient and rapid method of attaching targeting moieties to the surface of nanocarriers.