A series of well-defined amphiphilic comb poly (ether amine)s (acPEAs) were successfully synthesized through nucleophilic addition/ring-opening reaction of commercial available poly(propylene glycol) (PPO) diglycidyl ether and Jeffamine L100, followed by esterification of hydroxyl groups in backbone by alkyl carboxylic acid with different chain length. acPEAs are comprised of hydrophilic short PEO chains and hydrophobic alkyl chains as comb chains, which are grafted on PPO backbone alternately to form well-defined structure. With the very low critical micelle concentration (CMC) of around 3.0 x 10(-3) g/L, the obtained acPEAs can self-assemble into stable nanomicelles, whose aggregation is responsive to temperature, pH, and ionic strength with tunable cloud point (CP). The CP of acPEAs' aqueous solution increases with the decrease of the length of graft alkyl chains, the decrease of pH value, and the decrease of ionic strength. A transition behavior in the responsive aggregation of micelles formed by acPEA8 and acPEA10 in aqueous solution, especially at low pH value (<7.0), was observed, which was also revealed by DLS results. (C) 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3468-3475, 2010