A novel EGFR-targeted gene delivery system based on complexes self-assembled by EGF, DNA, and activated PAMAM dendrimers
Zhe Yin*, Nan Liu*, Mingshu Ma, Lan Wang, Yanli Hao, Xiaoning Zhang Laboratory of Pharmaceutics, School of Medicine, Tsinghua University, Beijing, China*These authors contributed equally to this workAbstract: Epidermal growth factor receptor (EGFR)-targeted gene delivery is a promising approach in g...
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Dove Medical Press
2012
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oai:doaj.org-article:d72ff3dc9f614ff78775c0de711036912021-12-02T00:12:17ZA novel EGFR-targeted gene delivery system based on complexes self-assembled by EGF, DNA, and activated PAMAM dendrimers1176-91141178-2013https://doaj.org/article/d72ff3dc9f614ff78775c0de711036912012-08-01T00:00:00Zhttp://www.dovepress.com/a-novel-egfr-targeted-gene-delivery-system-based-on-complexes-self-ass-a10817https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Zhe Yin*, Nan Liu*, Mingshu Ma, Lan Wang, Yanli Hao, Xiaoning Zhang Laboratory of Pharmaceutics, School of Medicine, Tsinghua University, Beijing, China*These authors contributed equally to this workAbstract: 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 nonactivated 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.Keywords: activated dendriplexes, transfection efficiency, EGFR targeting, self-assembled EGF modificationYin ZLiu NMa MWang LHao YZhang XDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 4625-4635 (2012) |
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Medicine (General) R5-920 |
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Medicine (General) R5-920 Yin Z Liu N Ma M Wang L Hao Y Zhang X A novel EGFR-targeted gene delivery system based on complexes self-assembled by EGF, DNA, and activated PAMAM dendrimers |
| description |
Zhe Yin*, Nan Liu*, Mingshu Ma, Lan Wang, Yanli Hao, Xiaoning Zhang Laboratory of Pharmaceutics, School of Medicine, Tsinghua University, Beijing, China*These authors contributed equally to this workAbstract: 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 nonactivated 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.Keywords: activated dendriplexes, transfection efficiency, EGFR targeting, self-assembled EGF modification |
| format |
article |
| author |
Yin Z Liu N Ma M Wang L Hao Y Zhang X |
| author_facet |
Yin Z Liu N Ma M Wang L Hao Y Zhang X |
| author_sort |
Yin Z |
| title |
A novel EGFR-targeted gene delivery system based on complexes self-assembled by EGF, DNA, and activated PAMAM dendrimers |
| title_short |
A novel EGFR-targeted gene delivery system based on complexes self-assembled by EGF, DNA, and activated PAMAM dendrimers |
| title_full |
A novel EGFR-targeted gene delivery system based on complexes self-assembled by EGF, DNA, and activated PAMAM dendrimers |
| title_fullStr |
A novel EGFR-targeted gene delivery system based on complexes self-assembled by EGF, DNA, and activated PAMAM dendrimers |
| title_full_unstemmed |
A novel EGFR-targeted gene delivery system based on complexes self-assembled by EGF, DNA, and activated PAMAM dendrimers |
| title_sort |
novel egfr-targeted gene delivery system based on complexes self-assembled by egf, dna, and activated pamam dendrimers |
| publisher |
Dove Medical Press |
| publishDate |
2012 |
| url |
https://doaj.org/article/d72ff3dc9f614ff78775c0de71103691 |
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