Self-assembly triggered by self-assembly: Optically active, paramagnetic micelles encapsulated in protein cage nanoparticles

In this contribution, optically active and paramagnetic micelles of the ligand 1,4,7,10-tetraaza-1-(1-carboxymethylundecane)-4,7,10-triacetic acid cyclododecane (DOTAC10) have been incorporated inside capsids of the cowpea chlorotic mottle virus (CCMV) protein through a hierarchical process of self-assembly triggered by self-assembly. The DOTAC10 ligand was used to complex Gd^III, in order to form paramagnetic micelles, as well as to encapsulate an amphiphilic Zn^II phthalocyanine (ZnPc) dye that optically confirmed the encapsulation of the micelles. The incorporation of ZnPc molecules in the paramagnetic micelles led to high capsid loading of both Gd^III and ZnPc, as the micelles were stabilized by the amphiphilic dye encapsulation. The resulting protein cage nanoparticles (PCNs) show an improved r₁ relaxivity, suggesting the possible use of these nanostructures as contrast agents (CAs) for magnetic resonance imaging (MRI). Since the encapsulated ZnPc dye also has a potential therapeutic value, the present results represent a first step towards the consecution of fully self-assembled PCNs for multimodal imaging and therapy.