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https://doi.org/10.1016/j.biomaterials.2013.10.044
Title: | Supramolecular self-assembly forming a multifunctional synergistic system for targeted co-delivery of gene and drug | Authors: | Zhao, F. Yin, H. Li, J. |
Keywords: | Cationic polymer Cyclodextrin Folate-targeted delivery P53 Gene transfection Paclitaxel Redox-sensitive |
Issue Date: | Jan-2014 | Citation: | Zhao, F., Yin, H., Li, J. (2014-01). Supramolecular self-assembly forming a multifunctional synergistic system for targeted co-delivery of gene and drug. Biomaterials 35 (3) : 1050-1062. ScholarBank@NUS Repository. https://doi.org/10.1016/j.biomaterials.2013.10.044 | Abstract: | For developing a multifunctional bioreducible targeted and synergistic co-delivery system for anticancer drug paclitaxel (PTX) and p53 gene for potential cancer therapy, supramolecular self-assembled inclusion complex was prepared from PTX and star-shaped cationic polymer containing γ-cyclodextrin (γ-CD) and multiple oligoethylenimine (OEI) arms with folic acid (FA) conjugated via a disulfide linker. The inclusion complex, termed as γ-CD-OEI-SS-FA/PTX, was formed between PTX and the hydrophobic cavity of γ-CD core of the star polymer. The γ-CD-OEI-SS-FA/PTX complex further formed polyplexes with pDNA to give positively charged nanoparticles, becoming multifunctional supramolecular self-assembled co-delivery system for PTX and pDNA targeting to cancer cells that overexpress folate receptors (FRs). The results showed that the FA-targeted function induced higher gene transfection efficiency in the FR-positive KB cells. The redox-sensitive disulfide linker in the self-assembly system led to the detachment of the FA groups from the carrier after the FR-mediated endocytosis, which resulted in the release of the bound FRs followed by the recycling of the FRs from the cytosol onto the cell membrane surface, facilitating continuous FR-mediated endocytosis to achieve enhanced gene transfection. In addition, the complexed PTX was co-delivered to the cells with pDNA, which further enhanced the gene transfection even at low N/P ratios in the FR-positive KB cells. Further, the efficient delivery of wild-type p53 gene resulted in large cell population at sub G1 and G2/M phases, inducing significant cell apoptosis. Therefore, the multifunctional γ-CD-OEI-SS-FA/PTX self-assembly system with the synergistic effects of redox-sensitive FA-targeted and PTX-enhanced p53 gene delivery may be promising for cancer therapeutic application. © 2013 Elsevier Ltd. | Source Title: | Biomaterials | URI: | http://scholarbank.nus.edu.sg/handle/10635/67293 | ISSN: | 01429612 | DOI: | 10.1016/j.biomaterials.2013.10.044 |
Appears in Collections: | Staff Publications |
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