Targeting of the β2-adrenoceptor increases nonviral gene delivery to pulmonary epithelial cells in vitro and lungs in vivo

Elfinger, Markus; Geiger, Johannes; Hasenpusch, Günther; Üzgün, Senta; Sieverling, Nathalie; Aneja, Manish Kumar; Maucksch, Christof; Rudolph, Carsten

doi:10.1016/j.jconrel.2009.01.012

Cited by 45 publications

(26 citation statements)

References 23 publications

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“…Size measurement of different particles showed that increasing amount of ligand led to large hydrodynamic diameters of PEI-g-ILO/pCMV-luc particles up to 1 mm. Similar results were obtained by Elfinger et al when clenbuterol was coupled to PEI [13]. Particles with PEI-g-ILO F ILO ¼ 5 showed hydrodynamic diameters of less than 100 nm.…”

Section: Discussionsupporting

confidence: 88%

“…Studies are under way to conjugate ILO to biodegradable polymers. Unlike previous ligands, for example lactoferrin and clenbuterol which target bronchial and alveolar epithelial cells respectively [12,13], ILO as a ligand increases gene expression in both cell types. Thus, ILO presents itself as a highly promising ligand for topical PEI-based aerosol application for pulmonary gene transfer.…”

Section: Discussionmentioning

confidence: 80%

“…Nevertheless, its low gene transfer efficiency compared to viral vectors and its high toxicity due to high polymer doses needed for optimal gene transfer, limit the use of PEI, especially in terms of in vivo application. A variety of ligands including transferrin [10], folate [11], lactoferrin [12], clenbuterol [13], and growth factors such EGF [14], have been investigated to enhance PEI-mediated gene delivery in terms of cell specificity and reduction of cell toxicity.…”

Section: Introductionmentioning

confidence: 99%

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Targeting of the prostacyclin specific IP1 receptor in lungs with molecular conjugates comprising prostaglandin I2 analogues

et al. 2010

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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Targeting of the prostacyclin specific IP1 receptor in lungs with molecular conjugates comprising prostaglandin I2 analogues

et al. 2010

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“…Transfection efficiencies have been reported in epithelial cells using PEI [17], PEI grafted N-maleated chitosan copolymers [18], nanostructured lipid carrier with cetylated PEI and Lipofectamine 2000 [19], cationic gemini lipids [20], and poly(disulfide amine)s [21]. A comparison study using lung tumor and normal epithelial cells showed that Lipofectamine 2000 (cationic lipid) produced higher transfection efficiency than Effectene (cationic lipids) or SuperFect (activated-dendrimer) [22].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Transfection Efficiency of Nonviral Gene Transfer Reagents

2010

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This study compared six commercially available reagents (Arrest-In, ExpressFect, FuGENE HD, jetPEI, Lipofectamine 2000, and SuperFect) for gene transfection. We examined the efficiency and cytotoxicity using nine different cell lines (MC3T3-E1 mouse preosteoblasts, PT-30 human epithelial precancer cells, C3H10T1/2 mouse stem cells, MCF-7 human breast cancer cells, HeLa human cervical cancer, C2C12 mouse myoblasts, Hep G2 human hepatocellular carcinoma, 4T1 mouse mammary carcinoma, and HCT116 human colorectal carcinoma), and primary cells (HEKn human epidermal keratinocytes) with two different plasmid DNAs encoding luciferase or β-galactosidase in the presence or absence of serum. Maximal transfection efficiency in MC3T3-E1, C3H10T1/2, HeLa, C2C12, Hep G2, and HCT116 was seen using FuGENE HD, in PT-30, 4T1, and HEKn was seen using Arrest-In, and in MCF-7 was seen using jetPEI. Determination of cytotoxicity showed that the largest amount of viable cells was found after transfection with jetPEI and ExpressFect. These results suggest that FuGENE HD is the most preferred transfection reagent for many cell lines, followed by Arrest-In and jetPEI. These results may be useful for improving nonviral gene and cell therapy applications.

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“…Ligands that have been investigated for targeting purpose include antibodies [71][72][73][74], native ligands like proteins [3][4][5]75,76], peptide hormones [77], cholesterol [78] and vitamins [79][80][81][82][83], as well as artificial ligands such as small-molecule receptor agonists and antagonists [84][85][86][87], oligosaccharides [88][89][90], oligopeptides [91][92][93][94] and aptamers [12].…”

Section: Increasing the Specificity: Shielding And Targetingmentioning

confidence: 99%

Invading target cells: multifunctional polymer conjugates as therapeutic nucleic acid carriers

Lächelt

Wagner

2011

Front. Chem. Sci. Eng.

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Polymer-based conjugates are an interesting option and challenge for the design of nano-sized drugdelivery systems, as they require advanced conjugation chemistry and precise engineering. In the case of nucleic acid therapy, non-viral carriers face several biological barriers during the delivery process, namely 1) protection of the cargo from extracellular degradation, 2) avoidance of non-specific interactions with non-targeted tissues, 3) efficient entry into the target cells, 4) intracellular trafficking to the site of action and 5) cargo release. To take on these obstacles, multifunctional conjugates can act as "smart polymers" with microenvironment-sensing dynamics to facilitate the separate delivery steps. Synthesis of defined polymer architectures with precise functionalization enables structure-activity relationships to be investigated and the integration of key functions for efficient delivery. Thus bioresponsive polymer conjugates, which are equipped with molecular devices responding to the certain microenvironments within the delivery pathway (e. g. pH, redox potential, enzymes) can be assembled. This review focuses on the modular engineering and conjugation of multifunctional polymeric structures for the utilization as "tailor-made" nucleic acid carriers.

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Targeting of the β2-adrenoceptor increases nonviral gene delivery to pulmonary epithelial cells in vitro and lungs in vivo

Cited by 45 publications

References 23 publications

Targeting of the prostacyclin specific IP1 receptor in lungs with molecular conjugates comprising prostaglandin I2 analogues

Targeting of the prostacyclin specific IP1 receptor in lungs with molecular conjugates comprising prostaglandin I2 analogues

Comparison of Transfection Efficiency of Nonviral Gene Transfer Reagents

Invading target cells: multifunctional polymer conjugates as therapeutic nucleic acid carriers

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