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The controlled assembly of gold nanoparticles (AuNPs) with the sizeo fq uantum dots into predictable structures is extremely challenging as it requires the quantitatively and topologically precise placement of anisotropic domains on their small, approximately spherical surfaces.W e herein address this problem by using polyoxometalate leaving groups to transform 2nmd iameter gold cores into reactive building blocks with hydrophilic and hydrophobic surface domains whose relative sizes can be precisely tuned to give dimers,c lusters,a nd larger micelle-like organizations.U sing cryo-TEM imaging and 1 HDOSY NMR spectroscopy, we then providea nu nprecedented "solution-state" picture of howt he micelle-like structures respond to hydrophobic guests by encapsulating them within 250 nm diameter vesicles whose walls are comprised of amphiphilic AuNP membranes.T hese findings provide av ersatile new option for transforming very small AuNPs into precisely tailored building blocks for the rational design of functional water-soluble assemblies. [2] While considerable progress has been made in modifying the surfaces of relatively large or anisotropic gold cores, [3] this is not the case for very small, approximately spherical AuNPs, for which precise control over the formation of ligand-shell domains remains exceedingly difficult. [1] Fundamental to the rational design and synthesis of these superstructures is the development of AuNP building blocks with anisotropic ligand shells programmed to react in ap redictable fashion.