Peptide-based vectors mediated by avidin–biotin interaction for tumor targeted gene delivery

Abstract

Smart vectors with good biocompatibility and tumor-targeting ability for gene therapy have attracted much research interest. Here, through a simple but universal alternative, a novel self-assembled gene delivery system with optimized targeting ability was developed. TAT-PKKKRKV peptide (P) was synthesized as the primary component of a gene carrier. Avidin (A) and biotin-transferrin (T) of different molar ratios (1 : 1 and 1 : 5) were subsequently introduced into P–DNA complexes to form PAT–DNA complexes (PAT₁–DNA and PAT₂–DNA) mediated by avidin–biotin interaction. Both PAT₁–DNA and PAT₂–DNA complexes exhibited efficient DNA-binding abilities and low cytotoxicity. In an in vitro transfection assay, PAT₁–p53 complexes showed superior transfection capability in HeLa and HepG2 cells over COS-7 cells, primarily due to the over-expression of transferrin receptors on cancer cells. For PAT₂–DNA complexes, the target transfection ability decreased with the excess content of T. This study provides a unique and all-purpose strategy to fabricate functionalized gene vectors, and the results indicate that the PAT₁–p53 complex system has great potential for targeted cancer therapy.