Co-delivery of chemical drugs and therapeutic genes for synergistic therapy provides a promising strategy to treat devastating diseases. However, the real-time coordination patterns between chemical drugs and therapeu...Co-delivery of chemical drugs and therapeutic genes for synergistic therapy provides a promising strategy to treat devastating diseases. However, the real-time coordination patterns between chemical drugs and therapeutic genes remain poorly understood. Herein, the complexes of doxorubicin/graphene oxidepolyethyleneimine/p53 plasmid（Dox/GO-PEI/p53） were fabricated and employed to investigate the synergistic manner between Dox and p53 in the inhibition of He La cell growth. GO was conjugated with PEI to form the GO-PEI backbone as the delivery vector. The GO backbone provided surfaces with a high specific area to load Dox via the π-π stacking interaction, and was able to release Dox significantly faster at pH 5.0 than at pH 7.0, while the positively charged PEI section of GO-PEI could condense plasmids into GO-PEI/DNA nanoparticles via the electrostatic interaction. The nanoparticles efficiently mediated the transfection of DNA in He La cells, with lower cytotoxicity compared to PEI/DNA nanoparticles. Furthermore, the complexes of Dox/GO-PEI/p53 released Dox and expressed p53 gene in a sequential manner,and showed successive inhibition of the in vitro growth of He La cells. This type of drug/GO-PEI/DNA complex can be employed as a platform to investigate the coordination pattern between chemical drugs and therapeutic genes for tumor therapy.展开更多
基金supported by the National Natural Science Foundation of China(No.31670997)the Natural Science Foundation of Hunan Province(No.2015JJ1007)the Basic Research Program of Shenzhen City(No.JCYJ20160530193417959)
文摘Co-delivery of chemical drugs and therapeutic genes for synergistic therapy provides a promising strategy to treat devastating diseases. However, the real-time coordination patterns between chemical drugs and therapeutic genes remain poorly understood. Herein, the complexes of doxorubicin/graphene oxidepolyethyleneimine/p53 plasmid（Dox/GO-PEI/p53） were fabricated and employed to investigate the synergistic manner between Dox and p53 in the inhibition of He La cell growth. GO was conjugated with PEI to form the GO-PEI backbone as the delivery vector. The GO backbone provided surfaces with a high specific area to load Dox via the π-π stacking interaction, and was able to release Dox significantly faster at pH 5.0 than at pH 7.0, while the positively charged PEI section of GO-PEI could condense plasmids into GO-PEI/DNA nanoparticles via the electrostatic interaction. The nanoparticles efficiently mediated the transfection of DNA in He La cells, with lower cytotoxicity compared to PEI/DNA nanoparticles. Furthermore, the complexes of Dox/GO-PEI/p53 released Dox and expressed p53 gene in a sequential manner,and showed successive inhibition of the in vitro growth of He La cells. This type of drug/GO-PEI/DNA complex can be employed as a platform to investigate the coordination pattern between chemical drugs and therapeutic genes for tumor therapy.
