Cloaking Nanoparticles with Supramolecularly Constructed Protein Corona for Targeted Drug Delivery

Abstract

Cancer targeting nanomaterials have been extensively attempted by coating their surfaces with small molecules, peptides, proteins, and antibodies, but the tumor targeting and therapeutic efficacy still exhibits only a modest improvement due to deleterious interactions of nanomaterials with proteins (protein corona formation). Translating nanoparticle-based agents into clinical applications still remains a challenge due to the difficulty in regulating interactions on the interfaces between nanoparticles and biological systems. We develop a new targeting strategy for nanoparticles incorporated with a supramolecularly pre-coated recombinant fusion protein. Once thermodynamically stabilized in preferred orientations on the nanoparticles, the adsorbed fusion proteins as a corona minimize interactions with serum proteins to prevent the clearance of nanoparticles by macrophages, while ensuring systematic targeting functions in vitro and in vivo. This study provides new insight into the use of the supramolecularly built protein corona shield as a targeting agent through regulating the interfaces between nanoparticles and biological systems.