An Immunomodulatory DNA Hydrogel Based on Tetrahedral Framework Nucleic Acids for Treating Psoriasis

Area of Science:

• Biomaterials Science
• Immunology
• Dermatology

Background:

• Psoriasis is a chronic immune disorder with unmet therapeutic needs.
• Aberrant macrophage activation significantly impacts psoriasis pathogenesis.
• A safe, drug-free strategy to modulate macrophages is crucial for psoriasis treatment.

Purpose of the Study:

• To develop a novel DNA-based hydrogel (TDH) for psoriasis treatment.
• To investigate TDH's immunomodulatory effects on macrophages.
• To evaluate TDH's efficacy and safety in a preclinical psoriasis model.

Main Methods:

• Fabrication of tetrahedral framework DNA-based hydrogel (TDH) via self-assembly.
• In vitro assessment of TDH's effect on lipopolysaccharide (LPS)-activated macrophages.
• Transcriptome analysis to identify affected signaling pathways.
• In vivo evaluation of topical TDH application in an imiquimod-induced psoriasis mouse model.

Main Results:

• TDH demonstrated robust mechanical strength, injectability, and self-healing properties.
• TDH significantly downregulated pro-inflammatory cytokines and chemokines in activated macrophages.
• Transcriptome analysis revealed reprogramming of inflammatory signaling networks.
• Topical TDH application reduced psoriasis symptoms, immune cell infiltration, and epidermal hyperplasia in vivo without systemic toxicity.
• Immune homeostasis was successfully restored in the treated mice.

Conclusions:

• TDH is a biocompatible, programmable, and drug-free immunoregulatory platform.
• This study presents a novel nucleic acid-based biomaterial strategy for dermatological therapy.
• TDH shows significant therapeutic potential for psoriasis treatment.