Inflammatory stimulus-responsive polymersomes reprogramming glucose metabolism mitigates rheumatoid arthritis

Area of Science:

• Biomedical Engineering
• Immunology
• Metabolic Research

Background:

• Rheumatoid arthritis (RA) involves inflammation-resident cells shifting to glycolysis, worsening the condition.
• Targeting glucose metabolism offers a potential therapeutic strategy for RA by selectively inhibiting abnormal cell activity.
• Single glycolysis inhibitors like 2-deoxy-d-glucose (2-DG) can cause harmful oxidative stress, limiting their use.

Purpose of the Study:

• To design a novel drug delivery system for synergistic rheumatoid arthritis (RA) therapy.
• To co-deliver 2-deoxy-d-glucose (2-DG) and dexamethasone (Dex) using stimulus-responsive polymersomes (HTDD).
• To enhance drug bioavailability, achieve targeted delivery to inflamed sites, and mitigate RA progression.

Main Methods:

• Developed hyaluronic acid-triglycerol monostearate polymersomes (HTDD) for co-encapsulating 2-DG and Dex.
• Investigated HTDD's prolonged circulation, preferential accumulation in inflamed tissues, and stimulus-responsive drug release (pH and MMPs).
• Assessed the therapeutic efficacy of combined 2-DG and Dex delivery in mitigating RA symptoms.

Main Results:

• HTDD demonstrated prolonged circulation and targeted drug release at arthritic sites.
• 2-DG inhibited excessive cell proliferation and activation, while Dex improved 2-DG bioavailability and reduced oxidative stress.
• The combination therapy effectively suppressed inflammatory signaling and glycolysis, leading to significant RA mitigation.

Conclusions:

• Co-delivery of 2-DG and Dex via HTDD polymersomes offers a promising synergistic approach for RA therapy.
• Targeting glucose metabolism combined with anti-inflammatory treatment can effectively manage RA.
• This strategy highlights the potential of nanomedicine in reprogramming cellular metabolism for treating inflammatory diseases.