Magnetofection Enhances Lentiviral-Mediated Transduction of Airway Epithelial Cells through Extracellular and Cellular Barriers

Abstract

Gene transfer to airway epithelial cells is hampered by extracellular (mainly mucus) and cellular (tight junctions) barriers. Magnetofection has been used to increase retention time of lentiviral vectors (LV) on the cellular surface. In this study, magnetofection was investigated in airway epithelial cell models mimicking extracellular and cellular barriers. Bronchiolar epithelial cells (H441 line) were evaluated for LV-mediated transduction after polarization onto filters and dexamethasone (dex) treatment, which induced hemicyst formation, with or without magnetofection. Sputum from cystic fibrosis (CF) patients was overlaid onto cells, and LV-mediated transduction was evaluated in the absence or presence of magnetofection. Magnetofection of unpolarized H441 cells increased the transduction with 50 MOI (multiplicity of infection, i.e., transducing units/cell) up to the transduction obtained with 500 MOI in the absence of magnetofection. Magnetofection well-enhanced LV-mediated transduction in mucus-layered cells by 20.3-fold. LV-mediated transduction efficiency decreased in dex-induced hemicysts in a time-dependent fashion. In dome-forming cells, zonula occludens-1 (ZO-1) localization at the cell borders was increased by dex treatment. Under these experimental conditions, magnetofection significantly increased LV transduction by 5.3-fold. In conclusion, these results show that magnetofection can enhance LV-mediated gene transfer into airway epithelial cells in the presence of extracellular (sputum) and cellular (tight junctions) barriers, representing CF-like conditions.

Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy

“…Dextran, a cationic polymer, significantly increases transduction efficiency in human and mice primary NK cells transduced with lentiviruses [128]. Magnetofection improves lentivirusmediated gene delivery [129]. A modified 3D nanochannel-electroporation (NEP) method that can transfect 100-200 cells at a single-cell resolution has been developed [130].…”

Materials promoting viral gene delivery

“…488 Magnetite (Fe 3 O 4 ) as superparamagnetic iron oxide nanoparticles (SPIONs) have been reported in several studies as a vehicle to enhance gene delivery efficiencies, e.g. for delivery of AAV, 115,489 Ad, 487,490 oncolytic Ad, 491,492 LV, 484,493 and measles virus. 494 They are biocompatible and degradable and allow surface modification with various functionalities.…”

SPIONs Prepared in Air through Improved Synthesis Methodology: The Influence of γ-Fe2O3/Fe3O4 Ratio and Coating Composition on Magnetic Properties

“…Superparamagnetic iron oxide nanoparticles (SPIONs), the only clinically approved metal oxide nanoparticles (NPs) [1], emerge as medically interesting nanoparticles (NPs), being able to integrate multifunctional platforms and to perform multiple objectives such as imaging and therapy, (theranostics) or to perform a single advanced function through the incorporation of multiple functional units [2,3,4,5,6,7,8,9]. Concerning biomedical applications, SPIONs may be externally magnetically triggered, endowing a wide variety of purposes, namely: (i) site-specific magnetic targeting [10], (ii) target drug delivery of drugs and genes [11,12], (iii) negative contrast agents in magnetic resonance imaging (MRI) [13,14], (iv) hyperthermia treatment under alternating magnetic fields [15,16], (v) magnetic transfections [17], (vi) iron detection [18], (vii) chelation therapy [19], (viii) tissue engineering [20], (ix) stem cell tracking [21] and (x) cell separation and isolation [22].…”