4.7 Article

Efficient Delivery of Therapeutic siRNA by Fe3O4 Magnetic Nanoparticles into Oral Cancer Cells

Journal

PHARMACEUTICS
Volume 11, Issue 11, Pages -

Publisher

MDPI
DOI: 10.3390/pharmaceutics11110615

Keywords

magnetic nanoparticle; iron oxide; siRNA delivery; BCL2; BIRC5/survivin; oral cancer

Funding

  1. National Natural Science Foundation of China [31071916, 81703102]
  2. Scientific Research Program for Public Welfare of Liaoning Province [20170022]
  3. Foundation of China Medical University [XZR20160022]

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The incidence of oral cancer is increasing due to smoking, drinking, and human papillomavirus (HPV) infection, while the current treatments are not satisfactory. Small interfering RNA (siRNA)-based therapy has brought hope, but an efficient delivery system is still needed. Here, polyethyleneimine (PEI)-modified magnetic Fe3O4 nanoparticles were prepared for the delivery of therapeutic siRNAs targeting B-cell lymphoma-2 (BCL2) and Baculoviral IAP repeat-containing 5 (BIRC5) into Ca9-22 oral cancer cells. The cationic nanoparticles were characterized by transmission electronic microscopy (TEM), scanning electronic microscopy (SEM), dynamic light scattering (DLS), and vibrating sample magnetometer (VSM). By gel retardation assay, the nanoparticles were found to block siRNA in a concentration-dependent manner. The cellular uptake of the nanoparticle/siRNA complexes under a magnetic field was visualized by Perl's Prussian blue staining and FAM labeling. High gene silencing efficiencies were determined by quantitative real-time PCR and western blotting. Furthermore, the nanoparticle-delivered siRNAs targeting BCL2 and BIRC5 were found to remarkably inhibit the viability and migration of Ca9-22 cells, by cell counting kit-8 assay and transwell assay. In this study, we have developed a novel siRNA-based therapeutic strategy targeting BCL2 and BIRC5 for oral cancer.

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