Non-viral magnetic engineering of endothelial cells with microRNA and plasmid-DNA—An optimized targeting approach

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• 作者：Natalia Voronina ; MSc^a ; ^{natalia.voronina@med.uni-rostock.de" class="auth_mail" title="E-mail the corresponding author} ; Heiko Lemcke ; PhD^a ; ^{heiko.lemcke@uni-rostock.de" class="auth_mail" title="E-mail the corresponding author} ; Frank Wiekhorst ; PhD^b ; ^{Frank.Wiekhorst@ptb.de" class="auth_mail" title="E-mail the corresponding author} ; Jens-Peter Kü ; hn ; MD^c ; ^{kuehn@uni-greifswald.de" class="auth_mail" title="E-mail the corresponding author} ; Christian Rimmbach ; PhD^a ; Gustav Steinhoff ; PhD^a ; ^{gustav.steinhoff@med.uni-rostock.de" class="auth_mail" title="E-mail the corresponding author} ; Robert David ; PhD^a ; ^{davidrob@med.uni-rostock.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Non-viral delivery ; microRNA ; Cell engineering ; Magnetic nanoparticles ; Magnetic targeting ; MRI
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：12
• 期：8
• 页码：2353-2364
• 全文大小：2244 K

文摘

Genetic modulation of angiogenesis is a powerful tool for the treatment of multiple disorders. Here, we describe a strategy to produce modified endothelial cells, which can be efficiently magnetically guided.

First, we defined optimal transfection conditions with both plasmid and microRNA, using a polyethyleneimine/magnetic nanoparticle-based vector (PEI/MNP), previously designed in our group. Further, two approaches were assessed in vitro: direct vector guidance and magnetic targeting of transfected cells. Due to its higher efficiency, including simulated dynamic conditions, production of miR/PEI/MNP-modified magnetically responsive cells was selected for further detailed investigation. In particular, we have studied internalization of transfection complexes, functional capacities and intercellular communication of engineered cells and delivery of therapeutic miR. Moreover, we demonstrated that 10⁴ miRNA/PEI/MNP-modified magnetically responsive cells loaded with 0.37 pg iron/cell are detectable with MRI. Taken together, our in vitro findings show that PEI/MNP is highly promising as a multifunctional tool for magnetically guided angiogenesis regulation.