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Abstract
Small-interfering RNA (siRNA) can specifically silence disease gene expression, bringing hope for the effective treatment of gene-related diseases. However, its use in vivo is limited due to the lack of efficient carriers. Therefore, it is necessary to construct carriers with high efficiency, low toxicity and serum stability. As a promising polycation carrier, polyethylenimine (PEI) can be further modified with a fluorine-containing alkyl chain that brings hydrophobic and oleophobic characteristics to its surface. In this study, low molecular weight PEI 1.8 kDa was selected and fluorinated through an anhydride reaction, and the product was named PEIF. In vitro experiments have shown that PEIF/siRNA polyplexes have suitable and stable particle size and potential, compress nucleic acids at a very low w/w ratio, and have the ability to effectively silence specific genes with low cytotoxicity. Compared with the polyplexes prepared using PEI 25 kDa, the PEIF/siRNA polyplexes were more stable in serum, showed a better antiangiogenic ability in in vivo experiments, and had a better tumor inhibition effect. The above results indicate that fluoropolymers based on the fluorine effect have great potential as gene delivery carriers for tumor therapy.
Cancer treatment: Silencing critical genes without going viral
A polymer that helps nucleic acids sneak into cancer cells so they can suppress expression of critical genes shows beneficial effects in animal testing. Efforts to genetically re-program tumors using small RNA molecules have often used viruses as carriers capable of penetrating cell membranes. Wei-En Yuan from China’s Shanghai Jiao Tong University and colleagues have now developed a less hazardous type of carrier based on polymers modified to have Teflon-like properties. The team added fluorinated chains to a coating material known as polyethyleniamine to improve compatibility with the lipid-rich environment of cell membranes. Experiments in cell cultures demonstrated that with only a small amount of this new coating, RNA could be shuttled into tumors while preserving membrane structure. Subsequent trials in mice showed higher tumor inhibition rates than those seen with non-fluorinated polymer coatings.
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Details
1 Shanghai Jiao Tong University, Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293)
2 Shanghai Jiao Tong University, Department of Pulmonary and Critical Care Medicine, Rui Jin Hospital, School of Medicine, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293)