Targeted drug delivery using nanoparticles can minimize the side effects of conventional pharmaceutical agents and enhance their efficacy. However, 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. Here, we present 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 vitro and in vivo. This study provides insight into the use of the supramolecularly built protein corona shield as a targeting agent through regulating the interfaces between nanoparticles and biological systems.

One of the most fascinating subjects in areas such as nanoscience and biomimetic chemistry is concerned with the construction of novel supramolecular nanoscopic architectures with well defined shapes and functions. Supramolecular assemblies of aromatic rod molecules provide a facile entry into this area. Aromatic rigid rod molecules consisting of hydrophilic flexible chains, in aqueous solution can self-assemble into a variety of supramolecular structures through mutual interactions between aromatic rod molecules and water, including hydrophobic and hydrophilic interactions and π–π interaction. The supramolecular architecture in water can be manipulated by variation of the shape of the rigid segments, as well as the relative volume fraction of the flexible segment. The rigid aromatic segments have significant photonic and electronic properties. The self-assembly of aromatic rod molecules in water, therefore, can provide a strategy for the construction of well-defined and stable nanometer-size structures with chemical functionalities and physical properties as advanced materials for photonic, electronic and biological applications.

Achieving spatiotemporal control of molecular self-assembly associated with actuation of biological functions inside living cells remains a challenge owing to the complexity of the cellular environments and the lack of characterization tools. We present, for the first time, the organelle-localized self-assembly of a peptide amphiphile as a powerful strategy for controlling cellular fate. A phenylalanine dipeptide (FF) with a mitochondria-targeting moiety, triphenyl phosphonium (Mito-FF), preferentially accumulates inside mitochondria and reaches the critical aggregation concentration to form a fibrous nanostructure, which is monitored by confocal laser scanning microscopy and transmission electron microscopy. The Mito-FF fibrils induce mitochondrial dysfunction via membrane disruption to cause apoptosis. The organelle-specific supramolecular system provides a new opportunity for therapeutics and in-depth investigations of cellular functions.