Transdermal siRNA delivery via biomineralized nanoparticle-incorporated microneedles modulates cuproptosis-ferroptosis interaction for psoriasis therapy - PubMed
a day ago
- #Psoriasis
- #siRNA delivery
- #Microneedles
- Psoriasis is a chronic immune-mediated skin disorder linked to abnormal keratinocyte proliferation and inflammation.
- Dysregulation of copper transport is identified as a key metabolic driver in psoriasis.
- Solute carrier family 31 member 1 (SLC31A1) connects cuproptosis and ferroptosis, promoting psoriatic pathology.
- Upregulated SLC31A1 leads to copper accumulation and α-ketoglutarate elevation, activating KDM5B-dependent histone demethylation and repressing FTH1 transcription.
- A nanoparticle-incorporated microneedle system (CaP-siSlc31a1@MN) was developed for localized siRNA delivery to target SLC31A1.
- The microneedles ensure precise epidermal deposition, while biomineralized calcium phosphate nanoparticles facilitate intracellular uptake and siRNA release.
- In vitro and in vivo studies confirmed that CaP-siSlc31a1@MN effectively silenced Slc31a1, inhibited cuproptosis and ferroptosis, and suppressed IL17A-driven inflammation.
- This study introduces a transdermal gene-silencing nanoplatform integrating metabolic regulation with anti-inflammatory therapy for psoriasis treatment.