Arndt Stephanie, Unger Petra, Ivanova Irina, Bäumler Wolfgang, Drexler Konstantin, Berneburg Mark, Karrer Sigrid
Department of Dermatology, University Medical Center Regensburg, 93053 Regensburg, Germany.
Pharmaceuticals (Basel). 2025 Jun 17;18(6):907. doi: 10.3390/ph18060907.
Actinic keratosis (AK) occurs on sun-damaged skin and is considered a precursor to squamous cell carcinoma (SCC). Photodynamic therapy (PDT), using 5-aminolevulinic acid (ALA) and red light, is a common treatment for AK. However, its clinical efficacy for invasive tumors such as SCC is limited by the poor penetration and distribution of the photosensitizer. Cold atmospheric plasma (CAP), a partially ionized gas, increases skin permeability and exhibits anti-cancer properties through the generation of reactive oxygen species (ROS). In a previous study, CAP showed promising synergistic effects when combined with ALA-PDT for the treatment of SCC cells in vitro. The present study investigated the effects of combining CAP with ALA-PDT on cutaneous AK and SCC induced by ultraviolet B (UV-B) irradiation in SKH1 hairless mice. We compared various application sequences (CAP-ALA-red light, ALA-red light-CAP, and ALA-CAP-red light) against conventional ALA-PDT using visual, histological, and molecular assessments of the affected skin. The results demonstrated that combined treatments strongly inhibited the growth of UV-B-induced skin lesions. TUNEL staining revealed increased apoptosis following both single and combined therapies, while Ki-67 staining indicated reduced keratinocyte proliferation and diminished DNA damage in treated areas. mRNA expression analysis showed the upregulation of apoptosis-related genes (, ) alongside enhanced anti-tumor immune responses (, ) in the affected tissue samples. Notably, the combined treatment enhances the therapeutic effect, whereas the sequence of application does not seem to be relevant for therapeutic efficacy in vivo. Overall, these results suggest that CAP may enhance the anti-tumor effect of conventional ALA-PDT, supporting previous findings on SCC cells.
光化性角化病（AK）发生于受阳光损伤的皮肤，被认为是鳞状细胞癌（SCC）的前驱病变。使用5-氨基酮戊酸（ALA）和红光的光动力疗法（PDT）是治疗AK的常用方法。然而，其对SCC等侵袭性肿瘤的临床疗效受到光敏剂穿透性和分布较差的限制。冷大气等离子体（CAP）是一种部分电离的气体，可增加皮肤通透性，并通过产生活性氧（ROS）展现出抗癌特性。在先前的一项研究中，CAP与ALA-PDT联合用于体外治疗SCC细胞时显示出有前景的协同效应。本研究调查了CAP与ALA-PDT联合对SKH1无毛小鼠中紫外线B（UV-B）照射诱导的皮肤AK和SCC的影响。我们通过对受影响皮肤进行视觉、组织学和分子评估，将各种应用顺序（CAP-ALA-红光、ALA-红光-CAP和ALA-CAP-红光）与传统的ALA-PDT进行比较。结果表明，联合治疗强烈抑制了UV-B诱导的皮肤病变的生长。TUNEL染色显示，单药治疗和联合治疗后凋亡均增加，而Ki-67染色表明治疗区域角质形成细胞增殖减少且DNA损伤减轻。mRNA表达分析显示，受影响组织样本中凋亡相关基因（ ， ）上调，同时抗肿瘤免疫反应（ ， ）增强。值得注意的是，联合治疗增强了治疗效果，而应用顺序似乎与体内治疗效果无关。总体而言，这些结果表明CAP可能增强传统ALA-PDT的抗肿瘤作用，支持先前关于SCC细胞的研究结果。
