Efficient Gene Transfer into Macrophages and Dendritic Cells by in Vivo Gene Delivery with Mannosylated Lipoplex via the Intraperitoneal Route

Hattori, Yoshiyuki; Kawakami, Shigeru; Nakamura, Kazumi; Yamashita, Fumiyoshi; Hashida, Mitsuru

doi:10.1124/jpet.106.105098

Cited by 61 publications

(39 citation statements)

References 34 publications

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“…Isolated alveolar macrophages were cultured in RPMI 1640 supplemented with 10% heat-inactivated fetal bovine serum at a density of 2.1 ϫ 10 5 cells/cm 2 for 12 h before LPS challenge. In measuring the doseresponse of TNF␣ release, alveolar macrophages were coincubated with 1 g/ml LPS and 1 nM to 1 M DP formulations for 6 h. For the time course experiments, alveolar macrophages were stimulated with 1 g/ml LPS for 0.5 to 24 h. In the DP treatment, alveolar macrophages were coincubated with 1 g/ml LPS and 0.1 M free Dex solution, DP, or liposomal DP for a further 6 h. For the mannan inhibition study, 1 mg/ml mannan was added to the above mixture for competitive uptake mediated by mannose receptors (Hattori et al, 2006;Yeeprae et al, 2006;Wijagkanalan et al, 2008). After the indicated times, cytokine and chemokine protein levels in the supernatant were measured by ELISA (eBiosciences Inc., San Diego, CA).…”

Section: Methodsmentioning

confidence: 99%

“…We have reported previously macrophage-selective targeting carriers composed of novel mannosylated cholesterol derivatives, cholesten-5-yloxy-N-(4-((1-imino-2-D-thiomannosylethyl)amino)butyl)formamide (Man-C4-Chol), as a ligand for mannose receptors (Kawakami et al, 2000a;Hattori et al, 2006;Higuchi et al, 2006;Yeeprae et al, 2006). We have demonstrated the efficient targeting of mannosylated liposomes (Man-liposomes) to alveolar macrophages after intratracheal administration in rats (Wijagkanalan et al, 2008).…”

Section: Inhalation Of Lipopolysaccharide (Lps)mentioning

confidence: 99%

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Enhanced Anti-Inflammation of Inhaled Dexamethasone Palmitate Using Mannosylated Liposomes in an Endotoxin-Induced Lung Inflammation Model

Wijagkanalan¹,

Higuchi²,

Kawakami³

et al. 2008

Molecular Pharmacology

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Inhalation of bacterial endotoxin induces pulmonary inflammation by activation of nuclear factor B (NFB), production of cytokines and chemokines, and neutrophil activation. Although glucocorticoids are the drugs of choice, administration of free drugs results in adverse effects as a result of a lack of selectivity for the inflammatory effector cells. Because alveolar macrophages play a key role in the inflammatory response in the lung, selective targeting of glucocorticoids to alveolar macrophages offers efficacious pharmacological intervention with minimal side effects. We have demonstrated previously the selective targeting of mannosylated liposomes to alveolar macrophages via mannose receptor-mediated endocytosis after intratracheal administration. In this study, the anti-inflammatory effects of dexamethasone palmitate incorporated in mannosylated liposomes (DPML) at 0.5 mg/kg via intratracheal administration were investigated in lipopolysaccharide-induced lung inflammation in rats. DPML significantly inhibited tumor necrosis factor ␣, interleukin-1␤, and cytokine-induced neutrophil chemoattractant-1 levels, suppressed neutrophil infiltration and myeloperoxidase activity, and inhibited NFB and p38 mitogen-activated protein kinase activation in the lung. These results prove the value of inhaled mannosylated liposomes as powerful targeting systems for the delivery of anti-inflammatory drugs to alveolar macrophages to improve their efficacy against lung inflammation. Inhalation of lipopolysaccharide (LPS), which is a component of Gram-negative bacteria presenting as an environment pollutant, contributes to inflammation in the lung. The downstream signaling pathways after LPS stimulation include the activation of alveolar macrophages, which are key effector cells to release proinflammatory cytokines including tumor necrosis factor ␣ (TNF␣), interleukin-1␤ (IL-1␤) (Ulich et al., 1991), chemokines such as cytokine-induced neutrophil chemoattractant-1 (CINC-1) (Ulich et al., 1995), and activation of nuclear factor B (NFB) and p38 mitogen-activated protein kinase (p38MAPK). Thereafter, neutrophils are recruited into the lung and release protease enzymes, which trigger lung injury. Corresponding to these studies, depletion of alveolar macrophages by liposomal clodronate treatment completely suppressed the downstream signaling after LPS stimulation (Koay et al., 2002). These results indicate that alveolar macrophages play a key role in the inflammation to release proinflammatory cytokines and chemokines after LPS stimulation.Glucocorticoids (GCs) are the drugs of choice for treatment of lung inflammation via systemic or local administration. Although inhalation of free GC is a promising therapy with less systemic toxicity, the therapeutic efficacy has been ques-

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Section: Methodsmentioning

confidence: 99%

Section: Inhalation Of Lipopolysaccharide (Lps)mentioning

confidence: 99%

Enhanced Anti-Inflammation of Inhaled Dexamethasone Palmitate Using Mannosylated Liposomes in an Endotoxin-Induced Lung Inflammation Model

Wijagkanalan¹,

Higuchi²,

Kawakami³

et al. 2008

Molecular Pharmacology

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“…formamide (Man-C4-Chol), a galactosylated cholesterol derivative, to prepare mannosylated liposomes [179]. To deliver drugs into macrophage-and/or dendritic cell in various tissues, we investigated various administration routes including intravenous [179,[192][193][194][195][196][197], intraperitoneal [198][199][200][201], and intratracheal [202,203] administration.…”

Section: Development Of Mannosylated Liposomesmentioning

confidence: 99%

“…After intravenous administration, many mannosylated lipoplexes were rapidly taken up by the liver [194]. Therefore, the intraperitoneal administration route was selected to avoid rapid uptake by Kupffer cells and achieve sustained gene expression in macrophages and dendritic cells, but not Kupffer cells [198]. Following intraperitoneal administration of mannosylated lipoplexes into mice, high gene expression was observed in macrophages and dendritic cells from peritoneally exuded cells and the spleen.…”

Section: Nucleic Acid Deliverymentioning

confidence: 99%

Glycosylation-mediated targeting of carriers

Kawakami

Hashida

2014

Journal of Controlled Release

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For safe and effective therapy, drugs should be delivered selectively to their target tissues or cells at an optimal rate. Drug delivery system technology maximizes the therapeutic efficacy and minimizes unfavorable drug actions by controlling their distribution profiles. Ligand-receptor binding is a typical example of specific recognition mechanisms in the body; therefore, ligand-modified drug carriers have been developed for active targeting based on receptor-mediated endocytosis. Among the various ligands reported thus far, sugar recognition is a promising approach for active targeting because of their high affinity and expression. Glycosylation has been applied for both macromolecular and liposomal carriers for cell-selective drug targeting.Recently, the combination of ultrasound exposure and glycosylated bubble liposomes has been developed. In this review, recent advances of glycosylation-mediated targeted drug delivery systems are discussed.

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“…In addition AKT is a major mediator of cell survival through direct inhibition of pro-apoptotic signals such as Bad and the Forkhead family of transcription factors (Paez J et al, Cancer Treat Res 115: 145-167, 2003). In ESCs, PI3K-AKT pathway plays an important role in maintaining the undifferentiated state (Armstrong L et al, Hum Mol Genet 15: 1894-1913, 2006. To develop the method for the more efficient generation of hemangioblast from ESCs/iPSCs, we utilized common marmoset ESC lines (Cj11 and CM40), and inhibited PI3K-AKT pathway with the inhibitor, LY294002, in the process of differentiation with EB formation, and plated individual cells in MethoCult® H4435 supplemented with BMP4 and VEGF.…”

Section: Or-12 Enhancement Of the Anti-tumor Effect Of Combination Wmentioning

confidence: 99%

The 17th Annual Meeting 2011 Japan Society of Gene Therapy

2014

The Journal of Gene Medicine

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Cancer treatment has been improved by recent progress in multimodal treatments. However, only palliative therapies remain for patients who have disease that is refractory to standard therapies including surgery, chemotherapy, or radiotherapy. The development of novel therapies is an urgent social need for such refractory cases. Gene therapy has been considered to be one of the so-called fourth therapies for cancer treatment. Although several approaches have shown some benefit, their clinical efficacies have generally been insufficient and unpredictable. The development of a new strategy to induce and maintain antitumor effects for longer periods in predictable way is imminent. To establish a new generation of antitumor therapies, we conducted several phase I clinical studies of immune and cell therapies targeting metastatic solid tumors. Our first phase I study involved immune gene therapy using a GM-CSF gene-transduced autologous tumor vaccine for stage IV renal cell cancer. Our results showed that this new immune gene therapy was safe and induced tumor-specific immune reactions in patients. Two out of four patients survived for more than six years. However, the clinical antitumor effect, i.e., reducing the size of large tumor masses, was inadequate with this approach alone. To overcome this limitation, we next used a mouse tumor model to explore several combination therapies for enhancing GM-CSF gene therapy. Our results demonstrated the effectiveness of the combined use of the TARC and RANTES chemokine genes with the GM-CSF gene. In the clinical setting, we adopted new cell therapy methods, using tumor associated antigen (TAA)pulsed dendritic cells with cytotoxic T cells, involving the breakage of immune tolerance and the induction of TAA-specific immune responses. This phase I clinical trial is now underway and thus far no severe adverse events have been observed. The combination of GM-CSF gene therapy followed by novel immune cell therapy may be our next challenge. Our second gene therapy approach is oncolytic virotherapy, with current targets of measles virus and enterovirus. Our mouse tumor model studies demonstrated that both viruses would be promising candidates. Collectively, we hope that both immune gene therapy and virotherapy will cast a new light on the field of clinical cancer treatment in near future.Special Lecture I Viruses as Allies of Man: From Swords to PloughsharesInder Verma Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037-1002, USA At the beginning of the third millennium, man has an opportunity to fulfill the cherished goal of improving the lot of humankind. Newer modalities of medicine are being practiced and daily new breakthroughs are being reported. I would like to talk about gene therapy, a form of molecular medicine, which will have a major impact on human health. At present, gene therapy is being contemplated for both genetic and acquired diseases. These include hemophilia, cystic fibrosis, diabetes, canc...

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Efficient Gene Transfer into Macrophages and Dendritic Cells by in Vivo Gene Delivery with Mannosylated Lipoplex via the Intraperitoneal Route

Cited by 61 publications

References 34 publications

Enhanced Anti-Inflammation of Inhaled Dexamethasone Palmitate Using Mannosylated Liposomes in an Endotoxin-Induced Lung Inflammation Model

Enhanced Anti-Inflammation of Inhaled Dexamethasone Palmitate Using Mannosylated Liposomes in an Endotoxin-Induced Lung Inflammation Model

Glycosylation-mediated targeting of carriers

The 17th Annual Meeting 2011 Japan Society of Gene Therapy

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