Magnetic-silk/polyethyleneimine core-shell nanoparticles for targeted gene delivery into human breast cancer cells

Wenxing Song,David A Gregory,Haider Al-Janabi,Munitta Muthana,Zhiqiang Cai,Xiubo Zhao

doi:10.1016/j.ijpharm.2018.11.030

Wenxing Song, David A Gregory + Show 4 more

Open Access

https://doi.org/10.1016/j.ijpharm.2018.11.030

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Abstract

The lack of efficient and cost-effective methods for gene delivery has significantly hindered the applications of gene therapy. In this paper, a simple one step and cost effective salting-out method has been explored to fabricate silk-PEI nanoparticles (SPPs) and magnetic-silk/PEI core-shell nanoparticles (MSPPs) for targeted delivery of c-myc antisense oligodeoxynucleotides (ODNs) into MDA-MB-231 breast cancer cells. The size and zeta potential of the particles were controlled by adjusting the amount of silk fibroin in particle synthesis. Lower surface charges and reduced cytotoxicity were achieved for MSPPs compared with PEI coated magnetic nanoparticles (MPPs). Both SPPs and MSPPs were capable of delivering the ODNs into MDA-MB-231 cells and significantly inhibited the cell growth. Through magnetofection, high ODN uptake efficiencies (over 70%) were achieved within 20 min using MSPPs as carriers, exhibiting a significantly enhanced uptake effect compared to the same carriers via non-magnetofection. Both SPPs and MSPPs exhibited a significantly higher inhibition effect against MDA-MB-231 breast cancer cells compared to human dermal fibroblast (HDF) cells. Targeted ODN delivery was achieved using MSPPs with the help of a magnet, making them promising candidates for targeted gene therapy applications.

Highlights

Gene therapy has shown great potential for the treatment of many diseases (Zhao et al, 2007; Zhang et al, 2014; Zhang et al, 2016)
The medium was removed, and the cells were washed twice with PBS buffer before being replaced with 180 μl serum-free medium. 20 μl of silk-PEI nanoparticles (SPPs)-c-myc antisense oligodeoxynucleotide (ODN) or magnetic-silk/PEI core-shell nanoparticles (MSPPs)-ODN complex dispersions with different particle/ ODN mass ratios were added into each well
SPP or MSPP solutions (20 μl) with equivalent amount of particles used for complexation with ODNs were added into wells

Summary

Introduction

Gene therapy has shown great potential for the treatment of many diseases (Zhao et al, 2007; Zhang et al, 2014; Zhang et al, 2016). Efficient gene therapy requires the delivery of genes to the cell nucleus or cytoplasm replacing or regulating the defective genes (Zhang et al, 2014). PEI is able to destabilize the endosomal membrane by the ‘proton sponge effect’ to protect DNAs against degradation and facilitate the release of DNAs from endosomes into cytoplasm (Zhang et al, 2014; Wang et al, 2009; Dey et al, 2011; Xiang et al, 2007). Attempts have been made to improve targeting by developing PEI coated magnetic

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