Lipidoid-polymer hybrid nanoparticles loaded with TNF siRNA suppress inflammation after intra-articular administration in a murine experimental arthritis model

Jansen, Manon A. A.; Klausen, Lasse Hyldgaard; Thanki, Kaushik; Lyngsø, Jeppe; Pedersen, Jan Skov; Franzyk, Henrik; Nielsen, Hanne Mørck; Eden, Willem van; Dong, Mingdong; Broere, Femke; Foged, Camilla; Zeng, Xianghui

doi:10.1016/j.ejpb.2019.06.009

Cited by 49 publications

(34 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar results have been obtained with lipid-polymer hybrid nanoparticles loaded with siRNA directed against TNFα. Intra-articular injection, in an experimental arthritis mouse model, showed that this nanotherapy could efficiently suppress the inflammatory process, this effect being obtained with a low TNFα-siRNA dose (i.e 1 μg) [88].…”

Section: Nanomedicines For Gene Therapymentioning

confidence: 97%

Advanced nanomedicines for the treatment of inflammatory diseases

Brusini

Varna

Couvreur

2020

Advanced Drug Delivery Reviews

117

View full text Add to dashboard Cite

Inflammation, a common feature of many diseases, is an essential immune response that enables survival and maintains tissue homeostasis. However, in some conditions, the inflammatory process becomes detrimental, contributing to the pathogenesis of a disease. Targeting inflammation by using nanomedicines (i.e. nanoparticles loaded with a therapeutic active principle), either through the recognition of molecules overexpressed onto the surface of activated macrophages or endothelial cells, or through enhanced vasculature permeability, or even through biomimicry, offers a promising solution for the treatment of inflammatory diseases. After providing a brief insight on the pathophysiology of inflammation and current therapeutic strategies, the review will discuss, at a pre-clinical stage, the main innovative nanomedicine approaches that have been proposed in the past five years for the resolution of inflammatory disorders, finally focusing on those currently in clinical trials.

show abstract

Section: Nanomedicines For Gene Therapymentioning

confidence: 97%

Advanced nanomedicines for the treatment of inflammatory diseases

Brusini

Varna

Couvreur

2020

Advanced Drug Delivery Reviews

117

View full text Add to dashboard Cite

show abstract

“…Lipid-polymer hybrid nanoparticles (LPNs) have been demonstrated previously to exhibit effective functional delivery of siRNA in vitro [158] and therapeutic delivery of siRNA in vitro and in vivo [159]. This hybrid delivery system has also shown promising results for delivery of mRNA, with the mRNA being encapsulated in a hybrid nanoparticle composed of the lipid-like material N1, N3, N5-tris(2-aminoethyl)benzene-1,3,5-tricarboxamide (TT) in TT3:DOPE:Cholesterol:DMG-PEG2000 (1,2-dimyristoyl-sn-glycerol, methoxypolyethylene glycol) with a polymeric PLGA core [160].…”

Section: Lipid-polymer Hybrid Nanoparticlesmentioning

confidence: 99%

Opportunities and Challenges in the Delivery of mRNA-Based Vaccines

et al. 2020

Self Cite

View full text Add to dashboard Cite

In the past few years, there has been increasing focus on the use of messenger RNA (mRNA) as a new therapeutic modality. Current clinical efforts encompassing mRNA-based drugs are directed toward infectious disease vaccines, cancer immunotherapies, therapeutic protein replacement therapies, and treatment of genetic diseases. However, challenges that impede the successful translation of these molecules into drugs are that (i) mRNA is a very large molecule, (ii) it is intrinsically unstable and prone to degradation by nucleases, and (iii) it activates the immune system. Although some of these challenges have been partially solved by means of chemical modification of the mRNA, intracellular delivery of mRNA still represents a major hurdle. The clinical translation of mRNA-based therapeutics requires delivery technologies that can ensure stabilization of mRNA under physiological conditions. Here, we (i) review opportunities and challenges in the delivery of mRNA-based therapeutics with a focus on non-viral delivery systems, (ii) present the clinical status of mRNA vaccines, and (iii) highlight perspectives on the future of this promising new type of medicine.

show abstract

“…Because only MSU is used to induce arthritis [2,4], this model can simulate symptoms such as joint swelling, local joint temperature rise, and joint limitation in acute episodes of gouty arthritis, and can be viewed as a simple arthritis. Both IL-1β and IL-1beta are the important indicators [20,22].TNFα is the earliest and most important inflammatory medium produced by activated macrophages. It can activate neutrophils and lymphocytes, increase the permeability of vascular endothelial cells, regulate the metabolic activity of other tissues and promote the synthesis and release of other cytokines [24,25].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, in the use of MSUinduced arthritis, the production of detectable T TNFα and IL-1β is closely related to the onset of clinical symptoms. Although TNFα is not a diagnostic and therapeutic indicator of gout, it is a crucial indicator that cannot be ignored in human arthritis [22].…”

Section: Discussionmentioning

confidence: 99%

The effect of uricase on monosodium urate (MSU) crystallization, IL-1β and TNFα in monosodium urate-induced arthritis

Chen

Liang²,

Wang³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background : Although the symptoms of gouty arthritis could be controlled by clinical methods, it is often impossible to remove tophi from joints that cause acute gouty arthritis. Methods : In study, we injected a suspension of MSU into the knee joint of chicken, and then injected uricase solution into the joint after 4, 8 and 12 hours. Since the beginning of the experiment, we monitored the circumference of the diseased joint and local temperature change. Computer tomography(CT) examination was performed to examine the MSU in the knee joints and then measured the levels of TNFα and IL-1β in synovial fluid. Chicken knee joint fluid was collected under polarized light microscope to observe the condition of the crystals and measured the weight of MSU residued in synovial fluid. Finally, the chicken knee joint was dissected and the joint synovium was sliced. Results : The results showed that injection of MSU suspension into chicken knee joint, significantly increased IL-1β, TNFα levels (p<0.01), circumference of the joint (p<0.05) and the local skin temperature (p<0.05). Moreover, analysis of the joint fluid and synovial slice under the polarized light microscope revealed that crystals significantly reduced. Compared with groupⅡ(control group), the residual weight of MSU in the joint fluid of group Ⅲ and group Ⅳ is very small(p<0.05), but there is no significant difference between group Ⅲ and group Ⅳ(p＞0.05). Conclusions : The comprehensive analysis shows that the reaction process between uricase and MSU is similar to that uric acid. Therefore, it provides a new way for clinical treatment of acute gouty arthritis with fewer side effects and significant reduction in the frequency of attacks.

show abstract

Lipidoid-polymer hybrid nanoparticles loaded with TNF siRNA suppress inflammation after intra-articular administration in a murine experimental arthritis model

Cited by 49 publications

References 41 publications

Advanced nanomedicines for the treatment of inflammatory diseases

Advanced nanomedicines for the treatment of inflammatory diseases

Opportunities and Challenges in the Delivery of mRNA-Based Vaccines

The effect of uricase on monosodium urate (MSU) crystallization, IL-1β and TNFα in monosodium urate-induced arthritis

Contact Info

Product

Resources

About