Abstract

Recently, RNA interfering (RNAi) has become a promising approach for cancer therapy. However, the application of RNAi for clinics is still hindered due to the lack of safe and efficient carriers. In this study, a pH-responsive micelle based on polycaprolactone-block–poly 2-(dimethylamino)ethyl methacrylate (PCL-PDEM) cationic copolymer was developed to carry short interfering RNA (siRNA) for silencing interleukin 8 (IL-8) gene in hepatoma cancer cells. The transfection efficiency of the PCL-PDEM-siRNA/quantum dots (QDs) nanoplex has reached about 70%, and the expression level of IL-8 decreased about 63%. Furthermore, the codelivery of QDs and siRNA has been realized, which is beneficial to visualize the process of siRNA delivery. No considerable cytotoxicity from the nanoparticles has been observed, indicating that our responsive cationic micelle is potential in clinical trial for hepatoma cancer therapy.

Highlights

  • As one of the most deadly and the second most common cancers throughout the world, hepatoma cancer is estimated to claim 750,000 lives every year worldwide, 51% of which occur in China (Wang et al, 2014)

  • The molecular weight of poly 2-(dimethylamino)ethyl methacrylate (PDEM) block obtained from these of PCL and PCL-PDEM was 10877. These peaks indicated that PDEM had been successfully grafted onto PCL chains, which had potential to be used to prepare micelle as gene carriers

  • We have proposed a pH stimuli-responsive micelle based on PCL-PDEM copolymer to deliver short interfering RNA (siRNA) with high transfection efficiency for hepatoma cancer therapy

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Summary

Introduction

As one of the most deadly and the second most common cancers throughout the world, hepatoma cancer is estimated to claim 750,000 lives every year worldwide, 51% of which occur in China (Wang et al, 2014). The invention of RNAi has brought promises for gene therapy of cancer by using small interfering RNA (siRNA), which selectively silences specific targets (Seyhan, 2011). What’s more, free siRNA is unable to penetrate the cell membrane due to its negatively charged nature (Whitehead et al, 2009). To address these issues, the researchers developed a great deal of carriers to delivery siRNA into cytoplasm (Lin et al, 2013; Shi et al, 2014; Dim et al, 2015; Li et al, 2015; Fitzgerald et al, 2016; Warashina et al, 2016). The viral vectors possessed high transfection efficiency, as well as low production, high cost, and potential biosafety issues (Marshall, 1999)

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