Nanocrystal Self‐Assembly in Cells

Abstract

The control of interactions between nanomaterials and cells remains a biomedical challenge. We propose a strategy to modulate the intralysosomal distribution of nanoparticles through the design of 3D suprastructures built by hydrophilic nanocrystals coated with alkyl chains. We compare the intracellular fate of two water-dispersible architectures of self-assembled hydrophobic magnetic nanocrystals: hollow deformable shells (colloidosomes) or solid fcc particles (supraballs). These two self-assemblies display increased cellular uptake by tumor cells compared with dispersions of the water-soluble nanocrystal (NC) building blocks. Moreover, the self-assembly structures increase the nanocrystal density in lysosomes and close to the lysosome membrane. Importantly, the structural organization of nanocrystals in colloidosomes and supraballs is maintained in lysosomes up to eight days after internalization, whereas initially dispersed hydrophilic nanocrystals are randomly aggregated. Supraballs and colloidosomes are differently sensed by cells due to their different architectures and mechanical properties. Flexible and soft colloidosomes deform and spread along the biological membranes. In contrast, the more rigid supraballs remain spherical. By subjecting the internalized suprastructures to a magnetic field, they both align and form long chains. Overall, we highlight that mechanical and topological properties of the self-assemblies direct their intracellular fate, allowing the control intralysosomal density, ordering, and localization of nanocrystals.