A Gene Delivery Vector With Encapsulated9B9Monoclonal Antibody For Target Therapy

Objective To enhance tumor-targeting abilities and therapeutic efficiency, an envelop-type gene nanocomplex with encapsulated9B9monoclonal antibody was herein designed. By using the therapeutic AChE gene, it was found that the PP9mN complexes significantly enhanced the anti-tumor effect.Methods The copolymers PHPA was formed as backbone by branch-PEI600cross-linked to poly-aspartic acid via Carbonyldiimidazole (CDI). Copolymers were characterized with1H-NMR, elemental analysis and GPC. The DNA binding capacity was determined by gel retardation assay. The PP9mN complex with the diameter of around300nm at its optimal weight ratio could be uptaken effectively by SMMC-7721cells. The cytotoxicity of the PP9mN complex was much lower than that of PEI25kD in SMMC-7721, HepG2, Bel-7404and COS-7cell lines. The PP9mN complex possessed the highly efficient in vitro gene delivery ability to the hepatocellular carcinoma cells. By tail intravenous injection of the PP9mN complex into the SMMC-7721xenograft mice model, the in vivo gene expression indicated that PP9mN could target to the tumor tissues effectively. By using the therapeutic AChE gene, it was found that the PP9mN complexes significantly enhanced the anti-tumor effect on tumor-bearing nude mice.Results Polyethylenimine-grafted-α,β-poly(N-3-hydroxypropyl)-DL-aspartamide (PHPA-PEI) was successfully synthesized, witch was used for complexing pDNA to form the PHPA-PEI/pDNA core, and then9B9mAb, an anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, was encapsulated to produce the envelop-type PHPA-PEI/pDNA/9B9mAb (PP9mN) complex. Such envelop-type gene complex with encapsulated monoclonal antibody should have great potential applications in liver cancer therapy.