Simplified biomimetic peptide-based vehicle for enhanced tumor penetration and rapid enzyme-induced drug release

Various nanodrug vehicles were well-designed with complicated functions for tumor therapy. However, the unsatisfactory tumor delivery efficiency and uncertain off-target release became the stumbling block of the nanodrugs on the way to the clinic. Inspired by efficient tumor targeting ability of albumin, we reported a simplified biomimetic peptide-based vehicle synthesized by copolymerizing L-glutamyl-L-lysine unit (EK dimer, an intrinsic surface peptide pair from albumin) with L-phenylalanine (F) to encapsulate doxorubicin (Dox). The zwitterionic peptide shell based on EK pair made the system exhibit prolonged blood circulation by mimicking the surface function of albumin, and enhanced tumor penetration by liquefying gelated water molecules in tumor extracellular matrix (ECM). Meanwhile, the overexpressed enzymes (cathepsin B, CB) in tumor can trigger the degradation of the peptide scaffold so as to rapidly release Dox. This simplified albumin-mimicking approach can provide a promising nanodrug delivering platform for clinical application.