# Roles for Exosomes in the Pathogenesis, Drug Delivery and Therapy of Psoriasis
## 5 Exosome-Based Therapeutic Applications in Soriasis
### Exosomes as Drug Delivery Systems for Psoriasis Treatment  
Currently, exosomes can also be used as delivery systems for psoriasis treatment due to their low immunogenicity, good stability, potent targeting and outstanding ability to fuse with target cells [93; 94]. In particular, the engineered exosomes have strong targeting potential and good histocompatibility and thus can deliver proteins, nucleic acids and/or drugs efficiently and accurately. Therefore, exosomes are a promising and novel delivery platform for targeted immunotherapy of psoriasis (Figure 3). [PERSON] et al. reported that UCMSC-exosomes could be used to deliver ASO-210 (antisense oligonucleotides of miR-210) for psoriasis treatment. They found that the average size and zeta potential of ASO-210-loaded UCMSC-exosomes were 115 nm and \(-\)22.48 mV,  
Figure 3: Exosomes serve as drug delivery systems for psoriasis treatment. Umbilical cord mesenchymal stem cell (UCMSC)-derived exosomes improve the delivery efficiency and stability of antisense oligonucleotides of miR-210 (ASO-210). ASO-210-loaded UCMSC-exosomes reduce psoriasis symptoms by suppressing Th17 cells and reducing enrichment of IL-17A, IFN-\(\gamma\), IL-6 and TNF-\(\alpha\) in lesional skin. Compared to free tofatitinib (TFC), TFC-loaded keratinocyte (KCs)-derived exosomes show higher suppressive effects on the expression of TNF-\(\alpha\), IL-23, IL-6 and IL-15 and better therapeutic effects on IMQ-induced psoriasis in mice. Compared to PD-LI’ exosomes, PD-LI’ MSC-derived exosomes enhance their therapeutic effects on psoriasis by restoring Th17/Teg balance and inhibiting the expression of IL-17A, IL-6 and TNF-\(\alpha\). PD-LI+ melanoma cell-derived exosomes can increase pristrinerin (Pri) uptake by CD4+ T cells, resulting in restoration of the Th17/Teg balance and decrease in abnormal proliferation of KCs. Annexin A1 (ANXA1)-loaded and fused exosomes retain the anti-inflammatory properties of M2 macrophages and ANXA1 protein. They upregulate the expression of M2 macrophage biomarker, arginase-1 (Arg-1), and reduce the levels of IL-18, IL-6 and TNF-\(\alpha\) in lesional skin. Finally, CX5461-loaded and fused exosomes target CCL20-rich inflamed skin through the chemotaxis function of CCR6 expressed on their surface and alleviate IMQ-induced psoriasis by reshaping the Th17/Teg balance and reducing the secretion of IL-17A, IL-23, IL-22, IL-18 and TNF-\(\alpha\). (Upward, vertical and red arrows denote increasing, while downward, vertical and red arrows indicate decreasing). respectively, with an average drug loading efficiency of 13.35% and a release efficiency of 94.02% within 48 h. ASO-210-loaded UCMSC-exosomes reduced psoriasis symptoms, exhausted Th17 cells and reduced enrichment of proinflammatory cytokines, such as IL-17A, IFN-\(\gamma\), IL-6 and TNF-\(\alpha\), in both spleen and skin lesions in vivo. More importantly, UCMSC-exosomes significantly improved the delivery efficiency and stability of ASO-210. Their findings revealed UCMSC-exosomes as promising delivery vehicles of antisense oligonucleotides for psoriasis treatment [95]. Recently, [PERSON] et al. chose a probe ultrasound method to load tofacitinib (TFC) into KC-exosomes (TFC-Exo) and further explored the anti-posoriatic effects of TFC-Exo. They demonstrated that TFC-Exo prepared using the probe ultrasound method had the highest drug loading efficiency (30.70%), absolute values of zeta potential (\(-8.7\) mV) and drug release efficiency (67.5%, 24 h). Importantly, compared to free TFC, TFC-Exo exerted higher suppressive effects on the expression of TNF-\(\alpha\), IL-23, IL-6 and IL-15 and better therapeutic effects on IMQ-induced psoriasis in mice. These findings suggest that exosomes can enhance the therapeutic effects of TFC on psoriasis [96]. Engineered exosomes can also be used as delivery systems for psoriasis treatment by increasing their precision targeting. For instance, the PD-1/PD-L1 checkpoint is one of the important pathways for inhibiting immune responses and maintaining immune homeostasis.