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.
Highlights
In most malignant tumors, sustained angiogenesis is considered to be an important marker of tumors[1]
Vascular endothelial growth factor (VEGF) is a highly specific growth factor that can promote the growth of vascular endothelial cells, and has been shown to be the most powerful and important factor involved in angiogenesis
The 19F NMR spectrum (Fig. 2b) was consistent with the Fourier transform infrared spectroscopy (FTIR) results, which confirmed the formation of a C-F bond, indicating the successful synthesis of PEIF
Summary
In most malignant tumors, sustained angiogenesis is considered to be an important marker of tumors[1]. VEGF can contribute to the survival of existing blood vessels, prevent the effective delivery of antitumor drugs to tumor tissues, and stimulate the growth of new blood vessels[2,3,4]. Inhibition of VEGF expression could lead to the inhibition of tumor-induced angiogenesis, thereby controlling tumor growth and metastasis. The application of siRNA is usually limited by its instability, easy degradation and failure, and difficulty of cellular uptake, among other factors, namely, the lack of an efficient delivery vector in vivo[8,9]. Nucleic acid drug delivery systems are mainly divided into two major categories: viral vectors and nonviral vectors[10]. Polycation carriers, a kind of nonviral vector that can polymerize various amino groups to form a substance capable of efficiently condensing nucleic acids, have been widely studied[12,13]
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