We describe the use of an amphiphilic macro molecular brush based on poly(ethylene glycol) (PEG) and poly(D,L-lactide) (PLA) as a stabilizer of hydrophobic solutes. The brush, which in solution adopted an extended backbone conformation consequent with excluded volume effects of the side chains, retained an elongated character in water following the hydrophobic collapse of PLA and the backbone triggered by a rapid change in solvent quality. However, in the presence of hydrophobic solutes at low concentrations in a homogeneous environment, the brush formed spherical unimolecular nanoparticles achieving high solute encapsulation efficiency. As solute content increased and exceeded what appears to be a limit for intramolecular solubilization, intermolecular assembly took place along with the formation of large aggregates, the properties of which were highly dependent on the solute. This first observation of the solute -triggered unimolecular collapse of an amphiphilic macromolecular brush should find important applications for the design of polymeric drug carriers whose "properties can be conveniently modified at the single molecule level.