Cloaking Nanoparticles with Supramolecularly Pre-Coated Protein Corona for Targeted Drug Delivery

Nanoscopic delivery vehicles capable of encapsulating drug molecules and releasing them in response to external stimuli are of great interest due to implications in therapeutic applications. However, the stability of encapsulation with self-assembled systems is limited during blood circulation and translating nanomedicines into clinical applications still remains a challenge due to the difficulty in regulating interactions on the interfaces between nanoparticles and biological systems. Thus, deliberate molecular design for stable encapsulation, targeting and triggered release is required. For this purpose, we have developed a facile synthetic method for highly stable, polymeric nanogels or polymer-caged hollow nanoparticles using a simple intra/inter-chain crosslinking reaction. We show a simple method for the preparation of biocompatible nanovehicles that provides the ability to encapsulate hydrophobic or hydrophilic drug molecules. Nano-carriers showed great stability to encapsulate drug molecules and drugs were only released inside cell. In addition, we showed a targeting strategy for nanoparticles incorporated with a supramolecularly pre-coated recombinant fusion protein in which HER2-binding affibody combines with glutathione-S-transferase. 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 vitroand in vivo. This study provides insight into the use of the supramolecularlybuilt protein corona shield as a targeting agent through regulating the interfaces between nanoparticles and biological systems