Abstract:

With the rapid development of modern gene technology and the achievement of human genome project, new understanding of the cause and treatment of various diseases comes to us. It is one of the hot spot of scientific research that construction of drug and gene co-delivery system to achieve effective treatment of cancer. In this research, the amphiphilic graft polymer polyethyleneimine-ferrocene(PEI-Fc) was synthesized as drug and gene carrier. PEI-Fc could form micelles in aqueous solution through the hydrophobic side groups of ferrocene. The hydrophobic anticancer drug doxorubicine(DOX) was loaded in micelles by oil/water(O/W) method. The size of micelles increased from 21 nm to 43 nm. Then, DOX and gene co-delivery nanoparticles were successfully constructed via electrostatic interaction of the PEI chains in the shell and DNA molecule. This doxorubicine and gene co-delivery complexes had a suitable size and positive surface charge. The co-delivery complexes could release DOX slowly in PBS buffer solution. Ferrocene was transformed from hydrophobic group to hydrophilic group with the adding of ceric ammonium nitrate. It leaded to the completely disruption of DOX-loaded micelles. Due to electrostatic interaction of PEI and DNA, the gene supramolecular complexes remained stable existence and showed commendable oxidation responsiveness. The consequences of in vitro cell culture experiments indicated that the co-delivery nanoparticles with positive charge were easily uptake by HepG2 cells and the cancer cells were killed with the sustaining release of DOX. And the PEI-Fc/DOX/DNA co-delivery nanoparticles in the cells could be transferred. In summary, the PEI-Fc/DOX/DNA co-delivery nanoparticles with redox stimulate-response could have potential use in clinical cancer therapy.

Key words: Stimulus-responsive, Doxorubicine, Gene, Co-delivery, Supramolecular assembly