A series of amphiphilic graft copolymers based on polyaspartamide were synthesized by successive aminolysis reactions of polysuccinimide using 2-diisopropylaminoethyl (DIP), O-(2-aminoethyl)-O′-methylpolyethylene glycol (PEG) and lauryl amine as pH-sensitive, hydrophilic and hydrophobic groups, respectively. The pH-dependent self-assembly behavior of the aqueous copolymer solution was investigated. Nano-aggregation, which was induced by a hydrophilic/hydrophobic shift of the DIP group in solution, occurred at a pH in the vicinity of the pKa of the DIP group. The mean diameter of the nano-aggregate could be modulated by changing the compositions of both pendants. The mean diameter of the nanoparticles increased with increasing solution pH from 6.5 to 8. The dissolution of paclitaxel into these amphiphilic nanoparticles was attempted and the pH-dependent release behavior was examined using a solvent-casting method. The results showed a significantly faster release of paclitaxel at pH = 6.5, which is a tumoral acidic pH, than at neutral physiological pH. These pH-sensitive PEGylated polyaspartamide derivatives have potential use as a tumor-targeting delivery system.