Novel Peptide–Polymer Conjugate with pH-Responsive Targeting/Disrupting Effects on Biomembranes

Conjugating polymers to peptides has become a new strategy of designing functional antitumor agents for their improved stability and enhanced activity. In this paper, a novel peptide–polymer conjugate PEPc–PMAA with pH responsiveness was designed and synthesized. The isoelectric point of PEPc was studied by dynamic light scattering for the targeting effect. Also, the transmittances of PMAA at different pHs were measured using an ultraviolet–visible spectrophotometer for determining the triggering pH of the disrupting effect. The results showed that PEPc–PMAA was hydrophilic under neutral conditions and changed to be amphiphilic composed of positively charged PEPc and hydrophobic PMAA under acidic conditions. The interactions between PEPc–PMAA and mimic cells were investigated by the measurements of membrane fluidity and cargo leakage from 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine and 1,2-dipalmitoyl-sn-glycerol-3-phospho-(1-rac-glycerol) (DPPG) liposomes. It proved that PEPc–PMAA caused a distinct membrane disturbance of the DPPG liposome at pH 5.5, resulting in more serious cargo leakage. Because of its targeting and disrupting effects on negatively charged biomembranes under acidic conditions, PEPc–PMAA showed its good potential as an antitumor agent.