Hur Ga-Hee, Ryu A-Reum, Kim Yong-Wan, Lee Mi-Young
Department of Medical Sciences, Soonchunhyang University, Asan 31538, Korea.
Department of Medical Biotechnology, Soonchunhyang University, Asan 31538, Korea.
Pharmaceutics. 2022 Apr 30;14(5):968. doi: 10.3390/pharmaceutics14050968.
Photodynamic therapy (PDT) has been used to treat cancers and non-malignant skin diseases. In this study, a chlorin e6-curcumin conjugate (Ce6-PEG-Cur), a combination of chlorin e6 (Ce6) and curcumin via a PEG linker, was used as a photosensitizer. The in vitro and in vivo effects of PDT using Ce6-PEG-Cur were analyzed in UVB-irradiated fibroblasts and hairless mice. The UVB-induced expression of MMPs was reduced in Hs68 fibroblast cells, and procollagen type Ⅰ expression was enhanced by Ce6-PEG-Cur-mediated PDT on a Western blotting gel. Moreover, UVB-induced collagen levels were restored upon application of Ce6-PEG-Cur-mediated PDT. Ce6-PEG-Cur-mediated PDT inhibited the expression of phosphorylated p38 in the MAPK signaling pathway, and it reduced the expression of phosphorylated NF-κB. In animal models, Ce6-PEG-Cur-mediated PDT inhibited the expression of MMPs, whereas procollagen type Ⅰ levels were enhanced in the dorsal skin of UVB-irradiated mice. Moreover, UVB-induced dorsal roughness was significantly reduced following Ce6-PEG-Cur-mediated PDT treatment. H&E staining and Masson's trichrome staining showed that the thickness of the epidermal region was reduced, and the density of collagen fibers increased. Taken together, Ce6-PEG-Cur-mediated PDT might delay and improve skin photoaging by ultraviolet light, suggesting its potential for use as a more effective photo-aging treatment.
光动力疗法(PDT)已被用于治疗癌症和非恶性皮肤病。在本研究中,一种通过聚乙二醇(PEG)连接子将二氢卟吩e6(Ce6)和姜黄素结合而成的二氢卟吩e6 - 姜黄素共轭物(Ce6 - PEG - Cur)被用作光敏剂。使用Ce6 - PEG - Cur进行光动力疗法的体外和体内效果在紫外线B(UVB)照射的成纤维细胞和无毛小鼠中进行了分析。在Hs68成纤维细胞中,UVB诱导的基质金属蛋白酶(MMPs)表达降低,并且在蛋白质免疫印迹凝胶上,Ce6 - PEG - Cur介导的光动力疗法增强了Ⅰ型前胶原的表达。此外,应用Ce6 - PEG - Cur介导的光动力疗法后,UVB诱导的胶原蛋白水平得以恢复。Ce6 - PEG - Cur介导的光动力疗法抑制了丝裂原活化蛋白激酶(MAPK)信号通路中磷酸化p38的表达,并降低了磷酸化核因子κB(NF - κB)的表达。在动物模型中,Ce6 - PEG - Cur介导的光动力疗法抑制了MMPs的表达,而在UVB照射小鼠的背部皮肤中Ⅰ型前胶原水平升高。此外,Ce6 - PEG - Cur介导的光动力疗法治疗后,UVB诱导的背部皮肤粗糙明显减轻。苏木精 - 伊红(H&E)染色和马松三色染色显示,表皮区域厚度减小,胶原纤维密度增加。综上所述,Ce6 - PEG - Cur介导的光动力疗法可能延缓并改善紫外线引起的皮肤光老化,表明其有潜力作为一种更有效的光老化治疗方法。