title: A novel EGFR-targeted gene delivery system based on complexes self-assembled by EGF, DNA, and activated PAMAM dendrimers.
abstract: Epidermal growth factor receptor (EGFR)-targeted gene delivery is a promising approach in gene therapy against EGFR-positive cancer. In addition, macromolecules, such as polyamidoamine (PAMAM) dendrimers, are potential nonviral gene carriers in this therapy because of their biocompatibility and modifiable features. To achieve the goal of selectively enhancing the transfection efficiency in EGFR-positive cancer cells, the researchers developed chemical approaches of EGF-dendrimer conjugate, which were effective but complicated. Studies on liposomes reveal that self-assembly is another effective but simpler approach in EGF modification. Moreover, properly activated PAMAM dendrimers exhibit higher transfection efficiency, but little research has been done on its ligand-modification. In this study, we developed and characterized a novel gene-delivery system based on activated EGF-dendriplexes, which is formed via self-assembly by EGF and complexes prepared by activated PAMAM dendrimer and plasmid DNA. Such complexes exhibit desired features compared to nonmodified or non-activated dendriplexes in vitro, including selective enhancement of transfection efficiency in EGFR-positive cells, decreased cytotoxicity, and low agonist effect. In vivo experimentation shows their EGFR-positive tumor targeted biodistribution and increased transfection efficiency at EGFR-positive tumors. Our results demonstrated that activated EGF-dendriplexes are safe and effective carriers for delivering gene drugs to EGFR-positive cells, which makes these complexes a promising targeted nonviral gene-delivery system for auxiliary cancer therapy.
authors.affiliation: Laboratory of Pharmaceutics, School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yin
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.forename: Mingshu
authors.initials: M
authors.lastname: Ma
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Hao
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry* / Q000493:pharmacokinetics; D050091:Dendrimers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004355:Drug Stability; D004815:Epidermal Growth Factor / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D019265:Spectroscopy, Near-Infrared; D014162:Transfection / Q000379:methods*
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004815:Epidermal Growth Factor; D004247:DNA; D066246:ErbB Receptors