# 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
Binding to PD-1 expressed on the surface of T cells can inhibit their proliferation and production of proinflammatory cytokines [97]. Hence, construction of exosomes with high PD-L1 expression through genetic engineering techniques can enhance their therapeutic effects on psoriasis. [PERSON] et al. constructed PD-L1\({}^{+}\) MSCs using lentiviral gene transfection technology and collected their exosomes for psoriasis treatment. These exosomes showed a spherical morphology with an average diameter of around 100 nm. In mouse models of IMQ-induced psoriasis, they observed a better therapeutic effect of PD-L1\({}^{+}\) MSC-exosomes compared to that of PD-L1\({}^{+}\) MSC-exosomes. PD-L1\({}^{+}\) MSC-exosomes significantly ameliorated the skin lesions and inflammation by restoring the immune balance of Th17/ Treg and inhibiting the expression of proinflammatory cytokines, such as IL-17A, IL-6, IFN-\(\gamma\), TNF-\(\alpha\) and IL-1\(\beta\). Thus, their findings imply that MSC-derived PD-L1\({}^{+}\) exosomes can be a potential delivery platform for psoriasis treatment [98]. Recently, [PERSON] et al. chose melanoma cell-derived PD-L1\({}^{+}\) exosomes for targeted delivery of pristimerin (Pri) to overactive cells in the inflammatory process of psoriasis via PD-1/PD-L1 interaction. They found that the size of Pri-loaded PD-L1\({}^{+}\) melanoma cell-derived exosomes (Pri@exo) was 89.56 nm, with an ultraviolet absorption peak at 460 nm. Compared to the Pri only group, Pri@exo substantially increased Pri uptake by CD\({}^{+}\) T cells and keratinocytes, significantly inhibited the proliferation of Th17 cells and promoted Treg differentiation in a psoriasis-like mouse model. Additionally, Pri@exo also decreased the abnormal proliferation of keratinocytes and production of pro-inflammatory cytokines in psoriaticic lesions by alleviating ferrotopsisticated changes in the psoriaticic skin. These engineered exosomes acted as a \"treat-to-target\" strategy for psoriasis treatment [99]. The fusion of exosomes with membranes of other cells or nanovesicles is an emerging strategy for psoriasis treatment. The fused vesicles not only maintain the bioactivity of drug-loaded exosomes but also retain the properties of cell membranes or nanovesicles. [PERSON] et al. fused annexin A1 (ANXA1)-overexpressing T cell-derived exosomes with M2 macrophage membranes to obtain ANXA1-loaded fused exosomes. These fused exosomes retained the anti-inflammatory properties of M2 macrophages as well as the macrophage reprogramming potential of ANXA1-overexpressing T cells. They found that the particle size and zeta potential of fused exosomes were 169 nm and -11 mV, respectively. The fused exosomes could be effectively engulfed by macrophages, thus promoting their M2 polarization in vitro. In addition, subcutaneous injection of the fused exosomes significantly upregulated the expression of M2 macrophage biomarker, arginase-1 (Arg-1), and reduced the levels of pro-inflammatory cytokines, including IL-18, IL-6 and TNF-\(\alpha\) in lesional skin, resulting in attenuation of the psoriasis-like skin inflammation [100]. Recently, [PERSON] et al. designed multifunctional fusion nanoviscicles that targeted skin lesions for the treatment of autoimmune skin diseases, including psoriasis. Firstly, they loaded CX5461, a small-molecule immunosuppression with anti-proliferative properties, into grapfreuit-derived exosome-like nanoviscicles (GEVs) via electroporation. Then, in order to enhance therapeutic efficiency and safety, the exosomes were fused with CCR6\({}^{+}\) nanoviscicles derived from membranes of engineered gingival-derived mesenchymal stem cells (GMSCs) to form FV@CX5461. They found that FV@CX5461 had a spherical-like morphology with the membrane structure, and that the average diameter was about 160 nm, with a zeta potential of around \(-21\) mV. Furthermore, the drug loading efficiency of FV@CX5461 was around 18%, while the in vitro drug release rate within 48 h was about 90%.