Inhibition of P42 MAPK Using A Nonviral Vector-Delivered siRNA Potentiates The Anti-Tumor Effect of Metformin in Prostate Cancer Cells

Monteagudo, S.; Pérez-Martínez, Francisco C.; Posadas, Inmaculada; Guerra, Javier Miguel Martín; Merino, Sonia; Sánchez-Verdú, Prado; Ceña, Valentı́n

doi:10.2217/nnm.11.61

Cited by 41 publications

(27 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For viability experiments, LDH release was used as an index of cellular death as previously described (29). Briefly, cells were cultured in 24-well culture plates and treated with vehicle (dimethyl sulfoxide; 1‰ DMSO) or 100 ng/mL LPS in the presence or absence of different concentrations of phosphorus or PAMAM dendrimers (diluted in complete RPMI 1640 culture medium) for 24 h. Supernatants were then collected and cells were washed with PBS and lysed with 0.9% Triton X-100 (vol/vol) in saline.…”

Section: Methodsmentioning

confidence: 99%

Neutral high-generation phosphorus dendrimers inhibit macrophage-mediated inflammatory response in vitro and in vivo

Posadas

Romero-Castillo

Brahmi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Inflammation is part of the physiological response of the organism to infectious diseases caused by organisms such as bacteria, viruses, fungi, or parasites. Innate immunity, mediated by mononuclear phagocytes, including monocytes and macrophages, is a first line of defense against infectious diseases and plays a key role triggering the delayed adaptive response that ensures an efficient defense against pathogens. Monocytes and macrophages stimulation by pathogen antigens results in activation of different signaling pathways leading to the release of proinflammatory cytokines. However, inflammation can also participate in the pathogenesis of several diseases, the autoimmune diseases that represent a relevant burden for human health. Dendrimers are branched, multivalent nanoparticles with a well-defined structure that have a high potential for biomedical applications. To explore new approaches to fight against the negative aspects of inflammation, we have used neutral high-generation phosphorus dendrimers bearing 48 (G3) or 96 (G4) bisphosphonate groups on their surface. These dendrimers show no toxicity and have good solubility and chemical stability in aqueous solutions. Here, we present data indicating that neutral phosphorus dendrimers show impressive antiinflammatory activities both in vitro and in vivo. In vitro, these dendrimers reduced the secretion of proinflammatory cytokines from mice and human monocytederived macrophages. In addition, these molecules present efficient antiinflammatory activity in vivo in a mouse model of subchronic inflammation. Taken together, these data suggest that neutral G3-G4 phosphorus dendrimers have strong potential applications in the therapy of inflammation and, likely, of autoimmune diseases.dendrimers | inflammation | innate immunity | air pouch | macrophage

show abstract

Section: Methodsmentioning

confidence: 99%

Neutral high-generation phosphorus dendrimers inhibit macrophage-mediated inflammatory response in vitro and in vivo

Posadas

Romero-Castillo

Brahmi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Afterwards, RNAse was inactivated by cooling the samples in an ice-cold water bath for 20 min followed by incubation at 4°C with heparin (0.5 USP units) to assure complete siRNA release from the nanoparticle as previously described [22]. Samples were then loaded onto an agarose gel, under the same experimental conditions as indicated above.…”

Section: Methodsmentioning

confidence: 99%

Second Generation Amphiphilic Poly-Lysine Dendrons Inhibit Glioblastoma Cell Proliferation without Toxicity for Neurons or Astrocytes

et al. 2016

Self Cite

View full text Add to dashboard Cite

Glioblastomas are the most common malignant primary brain tumours in adults and one of the most aggressive and difficult-to-treat cancers. No effective treatment exits actually for this tumour and new therapeutic approaches are needed for this disease. One possible innovative approach involves the nanoparticle-mediated specific delivery of drugs and/or genetic material to glioblastoma cells where they can provide therapeutic benefits. In the present work, we have synthesised and characterised several second generation amphiphilic polylysine dendrons to be used as siRNA carriers. We have found that, in addition to their siRNA binding properties, these new compounds inhibit the proliferation of two glioblastoma cell lines while being nontoxic for non-tumoural central nervous system cells like neurons and glia, cell types that share the anatomical space with glioblastoma cells during the course of the disease. The selective toxicity of these nanoparticles to glioblastoma cells, as compared to neurons and glial cells, involves mitochondrial depolarisation and reactive oxygen species production. This selective toxicity, together with the ability to complex and release siRNA, suggests that these new polylysine dendrons might offer a scaffold in the development of future nanoparticles designed to restrict the proliferation of glioblastoma cells.

show abstract

“…The lipid-based nanovectors include liposomes [19], stable nucleic acid lipid particles (SNALPs) [20], and lipidoid nanoparticles [21]. Non-lipid-based nanovectors contain chitosan [22], poly(amido amine) dendrimers [23], polyethylenimines [24], or other polymeric materials as the building blocks. Conjugates composed of lipid-polymers or polymer-polymers have also been frequently used for siRNA delivery [25].…”

Section: Systemic Delivery Of Gene Silencing Agents For Breast Cancermentioning

confidence: 99%

Delivery of gene silencing agents for breast cancer therapy

et al. 2013

View full text Add to dashboard Cite

The discovery of RNA interference has opened the door for the development of a new class of cancer therapeutics. Small inhibitory RNA oligos are being designed to specifically suppress expression of proteins that are traditionally considered nondruggable, and microRNAs are being evaluated to exert broad control of gene expression for inhibition of tumor growth. Since most naked molecules are not optimized for in vivo applications, the gene silencing agents need to be packaged into delivery vehicles in order to reach the target tissues as their destinations. Thus, the selection of the right delivery vehicles serves as a crucial step in the development of cancer therapeutics. The current review summarizes the status of gene silencing agents in breast cancer and recent development of candidate cancer drugs in clinical trials. Nanotechnology-based delivery vectors for the formulation and packaging of gene silencing agents are also described.

show abstract

Inhibition of P42 MAPK Using A Nonviral Vector-Delivered siRNA Potentiates The Anti-Tumor Effect of Metformin in Prostate Cancer Cells

Cited by 41 publications

References 59 publications

Neutral high-generation phosphorus dendrimers inhibit macrophage-mediated inflammatory response in vitro and in vivo

Neutral high-generation phosphorus dendrimers inhibit macrophage-mediated inflammatory response in vitro and in vivo

Second Generation Amphiphilic Poly-Lysine Dendrons Inhibit Glioblastoma Cell Proliferation without Toxicity for Neurons or Astrocytes

Delivery of gene silencing agents for breast cancer therapy

Contact Info

Product

Resources

About