title: A gene nanocomplex conjugated with monoclonal antibodies for targeted therapy of hepatocellular carcinoma.
abstract: To enhance tumor-targeting abilities and therapeutic efficiency, a monoclonal antibody-conjugated gene nanocomplex 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 nanoparticle, and then 9B9 mAb, an anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, was conjugated to produce the 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. 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 monoclonal antibody-conjugated gene complex should have great potential applications in liver cancer therapy.
authors.affiliation: Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, PR China.
authors.forename: J L
authors.initials: JL
authors.lastname: Wang
authors.forename: G P
authors.initials: GP
authors.lastname: Tang
authors.forename: J
authors.initials: J
authors.lastname: Shen
authors.forename: Q L
authors.initials: QL
authors.lastname: Hu
authors.forename: F J
authors.initials: FJ
authors.lastname: Xu
authors.forename: Q Q
authors.initials: QQ
authors.lastname: Wang
authors.forename: Z H
authors.initials: ZH
authors.lastname: Li
authors.forename: W T
authors.initials: WT
authors.lastname: Yang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D019938:Cyclin D1 / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D011108:Polymers; D019938:Cyclin D1; D011094:Polyethyleneimine; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D000110:Acetylcholinesterase