Gene delivery into human cancer cells by cationic lipid-mediated magnetofection

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• 作者：Srinath Govindarajan^a ; Kumiko Kitaura^b ; Makoto Takafuji^b ; ^c ; Hirotaka Ihara^b ; ^c ; K.S. Varadarajan^a ; Anant B. Patel^a ; Vijaya Gopal^a ; ^{vijaya@ccmb.res.in} ; ^{vg562000@gmail.com}
• 关键词：Liposomal magnetofection ; Magnetic nanoparticles ; Magnetic resonance imaging ; Gene delivery ; Cationic liposomes
• 刊名：International Journal of Pharmaceutics
• 出版年：2013
• 出版时间：25 March, 2013
• 年：2013
• 卷：446
• 期：1-2
• 页码：87-99
• 全文大小：2011 K

文摘

In this study, a combination of magnetic nanoparticles (MNPs) together with cationic lipid N,N-di-n-hexadecyl-N,N-dihydroxyethylammonium chloride formulated with colipid cholesterol, upon magnetofection, enhanced DNA uptake into human glioblastoma-astrocytoma, epithelial-like cell line U-87 MG, hepatocellular carcinoma Hep G2, cervical cancer HeLa and breast cancer MDA-MB-231 cells. Having confirmed this, we monitored uptake of plasmid DNA mediated by ternary magnetoplexes by fluorescence microscopy, flow cytometry and reporter gene expression assays in the presence and absence of a magnetic field. Our observations clearly indicate enhanced transfection efficiency in vitro, upon magnetofection, in the presence of serum as seen from ¦Â-Gal reporter gene expression. The observed activity in serum suggests the suitability of MNPs for in vivo applications. Further, we measured the transverse relaxation time (T₂) and obtained T₂-weighted MRI images of treated U-87 MG cells. T₂ determined for MNP-VP-Me₂₂ and MNP-VP-Et₂₂ corresponds to 22.6 ¡À 0.8 ms and 36.0 ¡À 2.1 ms, respectively, as compared to 47 ¡À 1.7 ms for control, suggesting their applicability in molecular imaging. Our results collectively highlight the potential of lipid-based approach to augment magnetic-field guided-gene delivery using MNPs and additionally towards developing intracellular molecular probes for magnetic resonance imaging.