Transfection of human macrophages by lipoplexes via the combined use of transferrin and pH-sensitive peptides

Simões, Sérgio; Slepushkin, Vladimir; Pretzer, Elizabeth; Dazin, Paul; Gaspar, Rogério; Lima, Maria C. Pedroso de; Düzgüneş, Nejat

doi:10.1002/jlb.65.2.270

Cited by 73 publications

(34 citation statements)

References 34 publications

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“…23 In macrophages, the present study showed that the gene expression and Gene Therapy uptake of plasmid DNA complexed with mannosylated liposomes was higher than with DOTMA/DOPE(1:1) and DC-Chol/DOPE(6:4) liposomes, and significantly inhibited by excess free mannose (Figure 3). In NIH3T3 cells lacking mannose receptors, 24 on the other hand, the transfection efficiency of DNA with mannosylated liposomes was less than that with DC-Chol/DOPE(6:4) liposomes and not inhibited by excess free mannose ( Figure 4).…”

Section: Discussionmentioning

confidence: 53%

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Mannose receptor-mediated gene transfer into macrophages using novel mannosylated cationic liposomes

et al. 2000

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Section: Discussionmentioning

confidence: 53%

“…23 In most cases, however, lipo- somes were coated with macromolecular ligands such as transferrin, immunoglobulins and asialoglycoproteins. In these cases, carriers are relatively easy to prepare, although there may be some problems involving factors such as reproducibility.…”

Section: Discussionmentioning

confidence: 99%

Mannose receptor-mediated gene transfer into macrophages using novel mannosylated cationic liposomes

et al. 2000

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“…We also tested this protocol for gene delivery on human monocyte-derived macrophages, a notoriously difficult cell type to transfect (32). HUVECs and A549 cells were grown to confluency and one well was used for cell count determination.…”

Section: Ad Infection Protocolsmentioning

confidence: 99%

Adenoviral Gene Delivery of Elafin and Secretory Leukocyte Protease Inhibitor Attenuates NF-κB-Dependent Inflammatory Responses of Human Endothelial Cells and Macrophages to Atherogenic Stimuli

Henriksen

Hitt

Xing

et al. 2004

The Journal of Immunology

135

121

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Atherosclerosis is a chronic inflammatory disease affecting arterial vessels. Strategies to reduce the inflammatory responses of endothelial cells and macrophages may slow lesion development and prevent complications such as plaque rupture. The human protease human neutrophil elastase (HNE), oxidized low density lipoprotein, LPS, and TNF-α were chosen as model stimuli of arterial wall inflammation and led to production of the chemokine IL-8 in endothelial cells. To counteract the activity of HNE, we have examined the effects of adenoviral gene delivery of the anti-elastases elafin, previously demonstrated within human atheroma, and murine secretory leukocyte protease inhibitor (SLPI), a related molecule, on the inflammatory responses of human endothelial cells and macrophages to atherogenic stimuli. We developed a technique of precomplexing adenovirus with cationic lipid to augment adenoviral infection efficiency in endothelial cells and to facilitate infection in macrophages. Elafin overexpression protected endothelial cells from HNE-induced IL-8 production and cytotoxicity. Elafin and murine SLPI also reduced endothelial IL-8 release in response to oxidized low density lipoprotein, LPS, and TNF-α and macrophage TNF-α production in response to LPS. This effect was associated with reduced activation of the inflammatory transcription factor NF-κB, through up-regulation of IκBα, in both cell types. Our work suggests a novel and extended anti-inflammatory role for these HNE inhibitors working as effectors of innate immunity to protect tissues against maladaptive inflammatory responses. Our findings indicate that elafin and SLPI may be gene therapy targets for the treatment of atheroma.

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“…In this regard, we and others have demonstrated that association of human transferrin to cationic liposome/DNA complexes enhances transfection in a large variety of cells, including dividing 18,19,27 and non-dividing cells. [28][29][30] As demonstrated in our recent work, 27 Tf-lipoplexes containing 1,2-dioleoyl-3-(trimethylammonium) propane (DOTAP)/cholesterol mediated the highest levels of transfection in oral cancer cells in culture, HSC-3 and SCC-7, when prepared at the 3/2 lipid/DNA ( ± ) charge ratio. We have also reported that delivery of HSV-tkexpressing plasmid to these cells mediated by Tflipoplexes followed by ganciclovir treatment resulted in essentially 100% cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Transferrin lipoplex-mediated suicide gene therapy of oral squamous cell carcinoma in an immunocompetent murine model and mechanisms involved in the antitumoral response

et al. 2008

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Suicide gene therapy has been used for the treatment of a variety of cancers. We reported previously the in vitro efficacy of the Herpes Simplex Virus Thymidine kinase (HSV-tk)/ganciclovir (GCV) system to mediate cytotoxicity in oral squamous cancer cells, using transferrin (Tf)-lipoplexes, prepared from cationic liposomes composed of 1,2-dioleoyl-3-(trimethylammonium) propane (DOTAP) and cholesterol. In the present study, we evaluated the antitumoral efficacy mediated by this lipoplex formulation in two suicide gene therapy strategies, HSV-tk/GCV and cytosine deaminase (CD)/5-fluorocytosine (5-FC), using a syngeneic, orthotopic murine model for head and neck squamous cell carcinoma. The cellular and molecular events associated with the antitumoral response elicited by both the therapeutic approaches were investigated by analyzing tumor cell death, tumor-infiltrating immune cells and tumor cytokine microenvironment. Significant tumor reduction was achieved upon intratumoral delivery of HSV-tk or CD genes mediated by Tf-lipoplexes, followed by intraperitoneal injection of GCV or 5-FC, respectively. Enhanced apoptosis, the recruitment of NK cells, CD4 and CD8 T-lymphocytes and an increase in the levels of several cytokines/chemokines were observed within the tumors. These observations suggest that suicide gene therapy with lipoplexes modifies the tumor microenvironment, and leads to the recruitment of immune effector cells that can act as adjuvants in reducing the tumor size.

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Transfection of human macrophages by lipoplexes via the combined use of transferrin and pH-sensitive peptides

Cited by 73 publications

References 34 publications

Mannose receptor-mediated gene transfer into macrophages using novel mannosylated cationic liposomes

Mannose receptor-mediated gene transfer into macrophages using novel mannosylated cationic liposomes

Adenoviral Gene Delivery of Elafin and Secretory Leukocyte Protease Inhibitor Attenuates NF-κB-Dependent Inflammatory Responses of Human Endothelial Cells and Macrophages to Atherogenic Stimuli

Transferrin lipoplex-mediated suicide gene therapy of oral squamous cell carcinoma in an immunocompetent murine model and mechanisms involved in the antitumoral response

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