A brief glimpse over the horizon for type 1 diabetes nanotherapeutics

Garciafigueroa, Yesica; Trucco, Massimo; Giannoukakis, Nick

doi:10.1016/j.clim.2015.03.016

Cited by 11 publications

(5 citation statements)

References 125 publications

(124 reference statements)

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“…Their physico-chemical properties can have impact on their biodistribution, tropism and toxicity. Independently from the outcome of the experimental studies, the potential utility of PNT in humans have raised concerns being of low biodegradability and having a fibrous structure with potential toxic effects [62]. In particular it was clearly shown their capacity to induce systemic immunosuppression through the release of cytokines and prostaglandins [63].…”

Section: Discussionmentioning

confidence: 99%

Use of short interfering RNA delivered by cationic liposomes to enable efficient down-regulation of PTPN22 gene in human T lymphocytes

Perri

Pellegrino

Ceccacci³

et al. 2017

PLoS ONE

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Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target. We aimed to develop novel wild type PTPN22 short interfering RNA duplexes (siRNA) and optimize their delivery into Jurkat T cells and PBMC by using liposomal carriers. Conformational stability, size and polydispersion of siRNA in lipoplexes was measured by CD spectroscopy and DLS. Lipoplexes internalization and toxicity evaluation was assessed by confocal microscopy and flow cytometry analysis. Their effect on Lyp expression was evaluated by means of Western Blot and confocal microscopy. Functional assays through engagement of TCR signaling were established to evaluate biological consequences of down-modulation. Both Jurkat T cells and PBMC were efficiently transfected by stable custom lipoplexes. Jurkat T cell morphology and proliferation was not affected. Lipoplexes incorporation was visualized in CD3+ but also in CD3- peripheral blood immunotypes without signs of toxicity, damage or apoptosis. Efficacy in affecting Lyp protein expression was demonstrated in both transfected Jurkat T cells and PBMC. Moreover, impairment of Lyp inhibitory activity was revealed by increase of IL-2 secretion in culture supernatants of PBMC following anti-CD3/CD28 T cell receptor-driven stimulation. The results of our study open the pathway to future trials for the treatment of autoimmune diseases based on the selective inhibition of variant PTPN22 allele using lipoplexes of siRNA antisense oligomers.

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Section: Discussionmentioning

confidence: 99%

Use of short interfering RNA delivered by cationic liposomes to enable efficient down-regulation of PTPN22 gene in human T lymphocytes

Perri

Pellegrino

Ceccacci³

et al. 2017

PLoS ONE

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“…NPs nature such as composition, size, shape, surface chemistry and protein-binding capability establishes NPs interactions, but it must be taken into account the individual difference and exposure route [195,196]. Systemic administration of NPs favors accumulation in the organs and tissues but it should be note that the size of particles influences which will be the accumulation site [197]. The immune response is dependent on the route of NPs entrance because different cells and molecules are present in different organs such as epithelium (i.e.…”

Section: Some Considerations To Keep In Mindmentioning

confidence: 99%

Immunotherapeutic nanoparticles: From autoimmune disease control to the development of vaccines

Mitarotonda¹,

Giorgi²,

Eufrásio-da-Silva³

et al. 2022

Biomaterials Advances

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“…1) favors accumulation in the organs and tissues such as the spleen, bone marrow, liver, lungs, and kidneys [6, 71]. The site of accumulation is also dependent on particle size as particles < 100 nm can evade clearance by the reticuloendothelial system (RES), a.k.a.…”

Section: Nanoparticles and The Immune Systemmentioning

confidence: 99%

“…Many of the former have been reviewed elsewhere [6, 71, 99], but certain examples merit repeating here. Phillips et al were able to incorporate antisense oligonucleotides for the costimulatory molecules CD40, CD80, and CD86 within PEG/PVP nano/microparticles, in order to convert DCs uptaking them to a suppressive phenotype [100].…”

Section: Tolerogenic Nanoparticlesmentioning

confidence: 99%

Tolerogenic Nanoparticles to Treat Islet Autoimmunity

Neef

Miller

2017

Curr Diab Rep

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Purpose of Review The current standard therapy for type 1 diabetes (T1D) is insulin replacement. Autoimmune diseases are typically treated with broad immunosuppression, but this has multiple disadvantages. Induction of antigen-specific tolerance is preferable. The application of nanomedicine to the problem of T1D can take different forms, but one promising way is the development of tolerogenic nanoparticles, the aim of which is to mitigate the islet-destroying autoimmunity. We review the topic and highlight recent strategies to produce tolerogenic nanoparticles for the purpose of treating T1D. Recent Findings Several groups are making progress in applying tolerogenic nanoparticles to rodent models of T1D, while others are using nanotechnology to aid other potential T1D treatments such as islet transplant and islet encapsulation. Summary The strategies behind how nanoparticles achieve tolerance are varied. It is likely the future will see even greater diversity in tolerance induction strategies as well as a greater focus on how to translate this technology from preclinical use in mice to treatment of T1D in humans.

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A brief glimpse over the horizon for type 1 diabetes nanotherapeutics

Cited by 11 publications

References 125 publications

Use of short interfering RNA delivered by cationic liposomes to enable efficient down-regulation of PTPN22 gene in human T lymphocytes

Use of short interfering RNA delivered by cationic liposomes to enable efficient down-regulation of PTPN22 gene in human T lymphocytes

Immunotherapeutic nanoparticles: From autoimmune disease control to the development of vaccines

Tolerogenic Nanoparticles to Treat Islet Autoimmunity

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