title: EGF-coated nano-dendriplexes for tumor-targeted nucleic acid delivery in vivo.
abstract: The clinical success of therapeutic DNA is still hindered due to the lack of effective delivery carriers. Here, we designed a tumor-targeted gene nano delivery system based on EGFR targeting strategy. Epidermal growth factor (EGF) was introduced to nano-complexes of PAMAM dendrimer and DNA via electrostatic interactions to form self-assembled PAMAM/DNA/EGF nano-complexes. The properties of self-assembled complexes were characterized by gel retardation assay and particle size and zeta potential analysis. Meanwhile, the toxicity of EGF-dendriplexes was evaluated by the MTT assay, which indicated that the complexes exhibited decreased cytotoxicity with the incorporation of EGF. We labeled polyamidoamine (PAMAM) dendrimers with FITC or a near-infrared (NIR) dye Lss670 and tested the cellular uptake in vitro and biodistribution in xenograft mouse tumor models. As compared to dendriplexes, the ternary EGF-dendriplexes showed a significantly higher cellular uptake into HepG2 cells due to the specific binding between EGF and EGF receptor (EGFR) over expressed on HepG2 cells, which resulted in the enhanced gene transfection efficiency. The biodistribution of EGF-dendriplexes in vivo was monitored with in vivo imaging technique, which indicated that EGF-dendriplexes enhanced EGFR-positive tumor-targeted biodistribution. These findings indicate that this novel nano-vector realized efficiently tumor-targeting gene delivery and high efficient gene expression in vivo, and it may possess a potential targeting gene delivery system in cancer therapy.
authors.affiliation: a School of Medicine, Tsinghua University , Beijing , China .
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: b Department of Gynaecology and Obstetrics , PLA Navy General Hospital , Beijing , China , and.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: a School of Medicine, Tsinghua University , Beijing , China .
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.affiliation: b Department of Gynaecology and Obstetrics , PLA Navy General Hospital , Beijing , China , and.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Li
authors.affiliation: a School of Medicine, Tsinghua University , Beijing , China .
authors.forename: Yanli
authors.initials: Y
authors.lastname: Hao
authors.affiliation: a School of Medicine, Tsinghua University , Beijing , China .|c Collaborative Innovation Center for Biotherapy, Tsinghua University , Beijing , China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism*; D018014:Gene Transfer Techniques; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D009696:Nucleic Acids / Q000737:chemistry / Q000235:genetics*; D014018:Tissue Distribution; D014162:Transfection / Q000379:methods*
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; D009696:Nucleic Acids; D004815:Epidermal Growth Factor; D004247:DNA; D066246:ErbB Receptors
keywords: Cancer therapy; EGF; dendriplexes; gene therapy; targeted delivery