Tumor Therapeutics Via Highly Efficient Mirna Delivery To Human Nasopharyngeal Cancer Cells By Multifunctional Magnetic Nanoparticles
NANOSCIENCE AND NANOTECHNOLOGY LETTERS(2020)
摘要
Efficient delivery of miRNA to target cells remains a significant challenge in clinical applications. In this research, we constructed a multifunctional miRNA (miR) delivery system composed of miR-expressing plasmids mediated by Fe3O4 -polyethyleneimine (PEI) nanoparticles (NPs). Fe3O4-PEImiR-expressing plasmid NPs targeting HIF-1 alpha or Survivin gene were respectively constructed and transfected into human nasopharyngeal carcinoma (NPC) CNE-II cells. The stability of Fe3O4 PEI-miR NPs was experimentally confirmed by serum protection assay. The antitumor effects of Fe3O4-PEI-miR NPs on CNE-II cells proliferation, apoptosis, and radiosensitivity were studied by employing the Cell Counting Kit (CCK-8) experiment, flow cytometry (FCM) analysis and radiosensitivity test. The antitumor efficiency of Fe3O4-PEI-miR NPs was investigated by qRT-PCR and Western blot. The Fe3O4-PE1-miR-expressing plasmid NPs were shown to be successfully established with favorable stability, enhanced biocompatibility and lower cytotoxicity, compared with Lipofectamine 2000. In addition, down-regulation of HIF-1 alpha or Survivin was validated to improve antitumor effects and radiosensitivity of NPC cells through proliferating cell nuclear antigen (PCNA). Transfection of miR-HIF-1 alpha/Survivin by Fe3O4-PEI NPs to CNE-II cells effectively inhibited NPC cell proliferation, induced cell apoptosis, and increased radiosensitivity. FFe3O4-PEI NPs were shown to be ideal gene carriers capable of novel gene therapy for treating human NPC.
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关键词
Fe3O4-PEI Nanoparticles,HIF-1 alpha,Survivin,miRNA,Nasopharyngeal Cancer
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