cis-Aconitic anhydride is used in the preparation of poly(amino acid)-containing copolymers with gradient pH-sensitive side groups initiated by the amino groups in methoxy poly(ethylene glycol)-block-poly(L-lysine). It is also involved in the preparation of pH-sensitive anti-tumor prodrug nanoparticles by conjugation with D-alfa-tocopheryl polyethylene glycol 1000 succinate (TPGS).