Chen Danyang, Zhang Yixuan, Long Wei, Chai Langjie, Myint Thazin Phoone, Zhou Wei, Zhou Ling, Wang Min, Guo Liang
Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Front Chem. 2023 Feb 16;11:1128255. doi: 10.3389/fchem.2023.1128255. eCollection 2023.
Photodynamic therapy (PDT) is widely used for the treatment of hypertrophic scars in clinical practice. However, the low transdermal delivery of photosensitizers in scar tissue and protective autophagy induced by Photodynamic therapy greatly reduces the therapeutic efficiency. Therefore, it is necessary to deal with these difficulties for overcoming obstacles in Photodynamic therapy treatment. In this study, a photosensitizer with photocatalytic performance was designed and synthesized using innovative MOFs (metal-organic frameworks). Additionally, the MOFs, together with an autophagy inhibitor chloroquine (CQ), was loaded in a high mechanical strength microneedle patch (MNP) for transdermal delivery. With these functionalized MNP, photosensitizers and chloroquine were delivered deep inside hypertrophic scars. Inhibition of autophagy increases the levels of reactive oxygen species (ROS) under high-intensity visible-light irradiation. Multiprong approaches have been used to remove obstacles in Photodynamic therapy and successfully enhance its anti-scarring effect. experiments indicated that the combined treatment increased the toxicity of hypertrophic scar fibroblasts (HSFs), downregulated the level of collagen type I expression as well as transforming growth factor-β1 (TGF-β1)expression, decreased the autophagy marker protein LC3II/I ratio, increased the expression of P62. experiments showed that the MNP had good puncture performance, and significant therapeutic effects were observed in the rabbit ear scar model. These results indicate that functionalized MNP has high potential clinical value.
光动力疗法(PDT)在临床实践中广泛用于治疗增生性瘢痕。然而,瘢痕组织中光敏剂的经皮递送效率低以及光动力疗法诱导的保护性自噬大大降低了治疗效果。因此,有必要解决这些难题以克服光动力疗法治疗中的障碍。在本研究中,使用创新的金属有机框架(MOFs)设计并合成了一种具有光催化性能的光敏剂。此外,将MOFs与自噬抑制剂氯喹(CQ)一起负载到具有高机械强度的微针贴片(MNP)中用于经皮递送。通过这些功能化的MNP,光敏剂和氯喹被递送至增生性瘢痕深部。自噬的抑制在高强度可见光照射下增加了活性氧(ROS)水平。已采用多种方法来消除光动力疗法中的障碍,并成功增强了其抗瘢痕作用。实验表明,联合治疗增加了增生性瘢痕成纤维细胞(HSFs)的毒性,下调了I型胶原蛋白表达水平以及转化生长因子-β1(TGF-β1)的表达,降低了自噬标记蛋白LC3II/I的比值,增加了P62的表达。实验表明,MNP具有良好的穿刺性能,并且在兔耳瘢痕模型中观察到了显著的治疗效果。这些结果表明功能化的MNP具有很高的潜在临床价值。