Rod-Shaped Nanotherapeutics Alleviate Rheumatoid Arthritis by Precisely Disrupting Platelet-Mediated Pathological...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Rheumatology

Background:

• Activated platelets (PLTs) amplify inflammation in rheumatoid arthritis (RA) through cellular crosstalk.
• Current PLT-targeting strategies neglect blood flow dynamics, limiting efficiency.
• Nanoparticle geometry can be optimized to control circulation behavior and improve targeting.

Purpose of the Study:

• To design and evaluate fucoidan-functionalized nanoplatforms with varying morphologies for PLT targeting.
• To investigate the morphology-dependent targeting efficiency and regulatory activity of nanoplatforms on PLTs.
• To assess the therapeutic efficacy of optimized nanoplatforms in an RA rat model.

Main Methods:

• Fabrication of fucoidan-functionalized nanoplatforms with different shapes.
• Assessment of nanoparticle-PLT co-localization using a microfluidic flow model.
• Analysis of signaling pathways (FAK, PI3K/AKT) in PLTs.
• In vivo evaluation of nanorod efficacy in arthritic rats.

Main Results:

• Rod-shaped nanoparticles demonstrated superior co-localization with endothelial-adherent PLTs in flow conditions.
• Nanoparticle morphology influenced the inhibition of FAK and PI3K/AKT signaling pathways.
• Intravenously administered resveratrol-loaded nanorods (PNR@Res) effectively targeted PLTs and accumulated in inflamed joints.
• PNR@Res treatment significantly alleviated RA symptoms in arthritic rats.

Conclusions:

• Nanoparticle geometry is a critical factor in achieving efficient PLT targeting and disrupting pathological crosstalk.
• Morphology-dependent mechanisms govern nanoparticle interactions with circulating PLTs in inflammatory diseases.
• Fucoidan-functionalized nanorods represent a promising strategy for RA therapy by modulating PLT behavior.