Mitochondria-targeted nanozyme system for psoriasis treatment

Area of Science:

• Biomaterials Science
• Nanotechnology
• Dermatology

Background:

• Psoriasis is a chronic inflammatory skin disease driven by oxidative stress and metabolic dysregulation.
• Current treatments often lack targeted delivery and multi-mechanism action.
• Identifying key molecular pathways and cellular players is crucial for effective therapeutic strategies.

Purpose of the Study:

• To develop a multifunctional liposomal hydrogel nanoplatform (CMH@lip@Res-TCeO2) for targeted psoriasis treatment.
• To investigate the combined antioxidant and anti-inflammatory effects of resveratrol and mitochondria-targeted cerium oxide nanozymes.
• To elucidate the underlying molecular mechanisms, including the ROS/mTOR/HIF-1α axis, in psoriasis pathogenesis.

Main Methods:

• Development of a thermo-responsive hydrogel incorporating liposomes with resveratrol and mitochondria-targeted cerium oxide nanozymes.
• Application of network pharmacology and transcriptomic analyses to identify therapeutic targets and pathways.
• Utilization of single-cell RNA sequencing to analyze cellular contributions to psoriasis.
• In vitro assessment of reactive oxygen species (ROS) suppression and pathway inhibition.
• In vivo evaluation in a mouse model of imiquimod-induced psoriasis-like skin inflammation.

Main Results:

• The CMH@lip@Res-TCeO2 nanoplatform demonstrated sustained transdermal delivery and enhanced local drug retention.
• Network pharmacology and transcriptomic analyses identified 36 key targets and the ROS/mTOR/HIF-1α axis.
• Single-cell RNA sequencing highlighted fibroblasts, keratinocytes, and neutrophils as key cell types.
• The nanoplatform effectively suppressed mitochondrial ROS, inhibited mTOR/HIF-1α signaling, reduced neutrophil extracellular trap (NET) formation, and improved keratinocyte function.
• In vivo studies showed significant reduction in inflammatory cytokines and improved skin histopathology in a psoriasis mouse model.

Conclusions:

• CMH@lip@Res-TCeO2 provides a promising nanotherapeutic strategy for psoriasis by regulating oxidative stress, metabolism, and inflammation at multiple levels.
• The study elucidates the critical role of the ROS/mTOR/HIF-1α axis in neutrophil regulation within psoriasis.
• This approach holds potential for treating psoriasis and other chronic inflammatory skin disorders.