Nanoparticles formed from amphiphilic block copolymers can be used as drug delivery vehicles for hydrophilic therapeutics. Poly(ethylene glycol) (PEG)-peptide copolymers were investigated for their self-assembling properties and as consequent potential delivery systems. Mono-and dihydroxy PEGs were functionalized with a pentavaline sequence bearing Fmoc end groups. The molecular weight of the PEG component was varied to evaluate copolymer size and block number. These di-and tri-block copolymers readily self-assemble in aqueous solution with critical aggregation concentrations (CACs) of 0.46-16.29 lM. At concentrations above the CAC, copolymer solutions form spherical assemblies. Dynamic light scattering studies indicate these aggregates have a broad size distribution, with average diameters between 33 and 127 nm. The copolymers are comprised b-conformations that are stable up to 80 C, as observed by circular dichroism. This peptide secondary structure is retained in solutions up to 50% MeOH as well. The triblock copolymers proved to be the most stable, with copolymers synthesized from 10 kDa PEG having the most stable particles. Loading of carboxyfluorescein at 2-5 mol % shows that these copolymers have the potential to encapsulate hydrophilic drugs for delivery applications. V C 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 49: 871-878, 2011