الفهرس 
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Abstract
RA is a systemic autoimmune disorder characterized by chronic inflammation of synovial tissue that results in irreversible joint damage. Gold nanoparticles (AuNPs) are promising new drugs for treatment of RA.
In this study, we have developed two shapes of AuNPs; AuNRs and AuNSs conjugated with three different surface Ligands; RGD, PEG and NLS respectively. AuNRs@RGD are AuNRs conjugated with Arginylglycylaspartic acid. AuNSs@PEG and AuNSs@NLS are AuNSs conjugated with polyethylene glycol and nuclear localization sequence peptide respectively. These surface ligands have been selected carefully based on their mode of action.
The present study was designed to evaluate the therapeutic efficacy of AuNPs with different shapes and ligands for the treatment of RA and compared them with the conventional (MTX) and biological (infliximab) treatments using CIA model.
Female adult Wistar rats (8 weeks old) were divided into 8 groups (10 rats/group). group 1 was kept as the control group. The remaining animals, from groups 2 to 8 were all subjected to collagen injection, representing the CIA model. group 2 remained without any treatment. Groups 3 and 4 received chemotherapeutic and biological treatment respectively. While, groups 5 to 8 were treated intra-articularly with different AuNPs. The design of the experimental groups was summarized as follow:
group 1: Normal control group.
group 2: Untreated-CIA group.
group 3: MTX-treated group.
group 4: Infliximab-treated group.
group 5: small AuNRs@RGD-treated group.
group 6: big AuNRs@RGD-treated group.
group 7: AuNSs@PEG-treated group.
group 8: AuNSs@NLS-treated group.
Results obtained from this study can be summarized as follows:
- Radiographic examination showed that AuNPs reduced joint space narrowing and bone erosion.
- Histopathological examination of rat ankle joint demonstrated that all AuNPs reduce bone and cartilage degeneration, AuNSs@NLS was the best AuNPs in resolving bone destruction and inflammation.
- Although, the Au accumulated in different organs, it didn’t induce any toxicity or tissue damage.
- AuNSs have no toxic effect as AuNRs.
- No harmful changes were observed in the liver and kidney function enzymes in all AuNPs-treated groups.
- AuNPs significantly down-regulated the expression of inflammatory and angiogenic mediators and induce the anti-inflammatory cytokines production.
- Nuclear-targeted AuNSs@NLS produce an optimal anti-rheumatic response as they increase the production of all studied anti-inflammatory cytokines besides the reduction of all pro-inflammatory ones.
In conclusion, nuclear membrane-targeting (AuNSs@NLS) were considered to be the most effective particles in RA treatment.