Spontaneous and instant formation of highly stable protein-nanoparticle supraparticle co-assemblies driven by hydrophobic interaction.

Recently, supraparticle protein-nanoparticle co-assemblies (or 'supraparticle co-assemblies' for short) have attracted considerable interest due to their fundamental and technological value. However, it remains challenging to form supraparticle co-assemblies with high stability. Here, we show that using hydrophobic interaction, instead of the previously used electrostatic and van der Waals interactions, as the primary driving force can lead to instant formation of exceptionally stable supraparticle co-assemblies with minimal external energy input. Our formation method of supraparticle co-assemblies simply involves mixing globular proteins ( e.g. , bovine serum albumin) with hydrophobic nanoparticles ( e.g. , hydrophobic magnetic nanoparticles and hydrophobic quantum dots) without significant energy input ( e.g. , sonication or stirring). Upon mixing of hydrophobic nanoparticles and proteins, the formation of supraparticle co-assemblies only takes <1 minute. Further incubation of the mixture for several hours results in a gradual increase of the size uniformity of supraparticle co-assemblies. The formed supraparticle co-assemblies have been colloidally stable for 6 months and counting, and can withstand harsh environments such as basic and acidic pH, high temperature, high dilution, and serum. Co-encapsulation of different sizes/types of nanoparticles is found to be feasible and the co-encapsulation number ratio of different nanoparticles is well-controlled by the feeding ratio. Proof-of-concept studies show the potential of the supraparticle co-assemblies for biological imaging, delivery, and modulation. The combination of very rapid formation, minimal energy consumption, highly stable products, and inexpensive raw materials of this hydrophobic interaction-driven process meets many of the main goals of 'ideal' nano-manufacturing. Thus, this process could serve as the foundation of ideal manufacturing of supraparticle co-assemblies.