Functionalized STAT1 siRNA Nanoparticles Regress Rheumatoid Arthritis in A Mouse Model

Scheinman, Robert I.; Trivedi, Ruchit; Vermillion, Sam; Kompella, Uday B.

doi:10.2217/nnm.11.90

Cited by 69 publications

(44 citation statements)

References 43 publications

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“…STAT1 was silenced leading to an increase in expression of Mrc-1 and IL-10 mRNA. 97 The above-mentioned studies have used antibodies, synthetic peptidomimetics, or RGD peptides for targeting. However, immunogenic effects of antibodies are well known, 98 cytotoxicity issues and safety issues of peptidomimetics are not yet established and RGD peptides are not specific against any rheumatoid markers.…”

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confidence: 99%

Molecular targets in arthritis and recent trends in nanotherapy

Roy¹,

Kanwar²,

Kanwar³

2015

IJN

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Due to its severity and increasing epidemiology, arthritis needs no description. There are various forms of arthritis most of which are disabling, very painful, and common. In spite of breakthroughs in the field of drug discovery, there is no cure for arthritis that can eliminate the disease permanently and ease the pain. The present review focuses on some of the most successful drugs in arthritis therapy and their side effects. Potential new targets in arthritis therapy such as interleukin-1β, interleukin-17A, tumor necrosis factor alpha, osteopontin, and several others have been discussed here, which can lead to refinement of current therapeutic modalities. Mechanisms for different forms of arthritis have been discussed along with the molecules that act as potential biomarkers for arthritis. Due to the difficulty in monitoring the disease progression to detect the advanced manifestations of the diseases, drug-induced cytotoxicity, and problems with drug delivery; nanoparticle therapy has gained the attention of the researchers. The unique properties of nanoparticles make them highly attractive for the design of novel therapeutics or diagnostic agents for arthritis. The review also focuses on the recent trends in nanoformulation development used for arthritis therapy. This review is, therefore, important because it describes the relevance and need for more arthritis research, it brings forth a critical discussion of successful drugs in arthritis and analyses the key molecular targets. The review also identifies several knowledge gaps in the published research so far along with the proposal of new ideas and future directions in arthritis therapy.

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confidence: 99%

Molecular targets in arthritis and recent trends in nanotherapy

Roy¹,

Kanwar²,

Kanwar³

2015

IJN

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“…RGD targeting improved siRNA uptake in the paw tissue of arthritic mice and increased delivery of nanoparticles into lungs. Animals treated with RGD-PLGA-STAT1-siRNA nanoparticles recovered while disease progressed in all control groups (Scheinman et al, 2011). Another approach to decrease the level of pro-inflammatory cytokines is to induce synthesis of anti-inflammatory cytokines.…”

Section: Anti-cytokine Activitymentioning

confidence: 98%

“…Functionalization of the nanoparticle surface with targeting moieties has allowed for some of these challenges to be addressed. For example, coating the nanoparticle surface with an Arg-Gly-Asp moiety (RGD) peptide specific to αVβ3 integrin ensured delivery of nanoparticles to the sites of active angiogenesis, which often accompanies inflammation (Scheinman et al, 2011).…”

Section: Anti-cytokine Activitymentioning

confidence: 99%

“…Cytokine production can also be significantly reduced by siRNA silencing expression of either the cytokine gene itself, or of components of the signalling pathways leading to activation of cytokine gene expression (Scheinman et al, 2011). Challenges common to therapeutic delivery of siRNA include lack of targeting, low potency, off-target toxicities and poor stability in biological matrices, all of which conceivably can be addressed through the use of nanocarriers.…”

Section: Anti-cytokine Activitymentioning

confidence: 99%

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Immunosuppressive and Anti-Inflammatory Properties of Engineered Nanomaterials

Ilinskaya

Dobrovolskaia

2016

Handbook of Immunological Properties of Engineered Nanomaterials

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Nanoparticle interactions with various components of the immune system are determined by their physicochemical properties such as size, charge, hydrophobicity and shape. Nanoparticles can be engineered to either specifically target the immune system or to avoid immune recognition. Nevertheless, identifying their unintended impacts on the immune system and understanding the mechanisms of such accidental effects are essential for establishing a nanoparticle's safety profile. While immunostimulatory properties have been reviewed before, little attention in the literature has been given to immunosuppressive and anti-inflammatory properties. The purpose of this review is to fill this gap. We will discuss intended immunosuppression achieved by either nanoparticle engineering, or the use of nanoparticles to carry immunosuppressive or anti-inflammatory drugs. We will also review unintended immunosuppressive properties of nanoparticles per se and consider how such properties could be either beneficial or adverse. LINKED ARTICLESThis article is part of a themed section on Nanomedicine. To view the other articles in this section visit http://dx

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“…[25][26][27][28] This slow-release, high-payload PLGA-NP system is also successful in the sustained delivery of small interfering RNAs. [29][30][31] Nanoparticles provide for enhanced cellular uptake and sustained delivery at the site of ocular administration. 32 The noncationic properties of PLGA NPs circumvent the issues of toxicity associated with cationic polymers.…”

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confidence: 99%

Nanoparticle-Mediated Delivery of shRNA.VEGF-A Plasmids Regresses Corneal Neovascularization

Qazi

Stagg

Singh

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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Functionalized STAT1 siRNA Nanoparticles Regress Rheumatoid Arthritis in A Mouse Model

Abstract: RGD functionalized PLGA nanoparticles encapsulating STAT1-targeted siRNAs are efficacious in the treatment of established arthritis, possibly through a selective inhibition of macrophage and dendritic cell activation.

Cited by 69 publications

References 43 publications

Molecular targets in arthritis and recent trends in nanotherapy

Molecular targets in arthritis and recent trends in nanotherapy

Immunosuppressive and Anti-Inflammatory Properties of Engineered Nanomaterials

Nanoparticle-Mediated Delivery of shRNA.VEGF-A Plasmids Regresses Corneal Neovascularization

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Functionalized STAT1 siRNA Nanoparticles Regress Rheumatoid Arthritis in A Mouse Model

Abstract: RGD functionalized PLGA nanoparticles encapsulating STAT1-targeted siRNAs are efficacious in the treatment of established arthritis, possibly through a selective inhibition of macrophage and dendritic cell activation.

Cited by 69 publications

References 43 publications

Molecular targets in arthritis and recent trends in&nbsp;nanotherapy

Molecular targets in arthritis and recent trends in&nbsp;nanotherapy

Immunosuppressive and Anti-Inflammatory Properties of Engineered Nanomaterials

Nanoparticle-Mediated Delivery of shRNA.VEGF-A Plasmids Regresses Corneal Neovascularization

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Product

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About

Molecular targets in arthritis and recent trends in nanotherapy

Molecular targets in arthritis and recent trends in nanotherapy