An Envelop-Type Gene Nanocomplex with Encapsulated Monoclonal Antibodies for Target Therapy of Hepatocellular Carcinoma

摘要

To enhance tumor-targeting abilities and therapeutic efficiency, an envelop-type gene nanocomplex with encapsulated monoclonal antibody was herein designed. The biodegradable cationic polyethylenimine-grafted- α,β-poly(N-3-hydroxypropyl)-DL-aspartamide (PHPA-PEI) was used for complexing pDNA to form the PHPA-PEI/pDNA core, and then 9B9 mAb, an anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, was encapsulated to produce the envelop-type PHPA-PEI/pDNA/9B9 mAb (PP9mN) complex. The PP9mN complex with the diameter of around 300 nm at its optimal weight ratio could be uptaken effectively by SMMC-7721 cells. The cytotoxicity of the PP9mN complex was much lower than that of PEI 25 kD in SMMC-7721, HepG2, Bel-7404 and COS-7 cell 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-7721 xenograft 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. Such envelop-type gene complex with encapsulated monoclonal antibody should have great potential applications in liver cancer therapy.