Photodynamic therapy (PDT) is a non-invasive treatment strategy that includes the combination of three components—a photosensitizer, a light source, and tissue oxygen. PDT can be used for the treatment of skin diseases such as squamous cell carcinoma. The photosensitizer used in this study is the naturally derived chlorophyll derivative chlorin e6 (Ce6), which was encapsulated in ultradeformable ethosomes. Singlet oxygen production by Ce6 upon laser light irradiation was not significantly affected by encapsulation into ethosomes. PDT of squamous cell carcinoma cells treated with Ce6 ethosomes triggered increased mitochondrial superoxide levels and increased caspase 3/7 activity, resulting in concentration- and light-dose-dependent cytotoxicity. Ce6 ethosomes showed good penetration into 3D squamous cell carcinoma spheroids, which upon laser light irradiation exhibited reduced size, proliferation, and viability. The PDT effect of Ce6 ethosomes was specific and showed higher cytotoxicity against squamous cell carcinoma spheroids compared to normal skin fibroblast spheroids. In addition, PDT treatment of squamous cell carcinoma xenografts grown on chorioallantoic membranes of chick eggs (CAM) exhibited reduced expression of Ki-67 proliferation marker and increased terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining, indicating reduced proliferation and activation of apoptosis, respectively. The results demonstrate that Ce6-loaded ethosomes represent a convenient formulation for photodynamic treatment of squamous cell carcinoma.

中文翻译：

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天然来源的载体，用于光动力治疗鳞状细胞癌：体外和体内模型。

光动力疗法（PDT）是一种非侵入性治疗策略，包括三部分的组合-光敏剂，光源和组织氧。PDT可用于治疗皮肤疾病，例如鳞状细胞癌。本研究中使用的光敏剂是天然衍生的叶绿素衍生物二氢卟酚e6（Ce6），它被包裹在超可变形的脂质体中。Ce6在激光辐照下产生的单线态氧并不受封装到核糖体中的影响。用Ce6核糖体处理的鳞状细胞癌细胞的PDT触发线粒体超氧化物水平的增加和胱天蛋白酶3/7活性的增加，从而导致浓度和光剂量依赖性细胞毒性。Ce6核糖体对3D鳞状细胞癌球体具有良好的渗透性，在激光照射下，其显示出减小的尺寸，增殖和生存力。与正常的皮肤成纤维细胞球体相比，Ce6核糖体的PDT效应具有特异性，并且显示出对鳞状细胞癌球体更高的细胞毒性。此外，PDT处理在鸡卵绒毛膜上生长的鳞状细胞癌异种移植物（CAM）表现出Ki-67增殖标志物的表达减少和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）染色增加，表明增殖和凋亡激活减少， 分别。结果表明，负载Ce6的核糖体代表了用于光动力治疗鳞状细胞癌的方便制剂。与正常的皮肤成纤维细胞球体相比，Ce6核糖体的PDT效应具有特异性，并且显示出对鳞状细胞癌球体更高的细胞毒性。此外，PDT处理在鸡卵绒毛膜上生长的鳞状细胞癌异种移植物（CAM）表现出Ki-67增殖标志物的表达减少和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）染色增加，表明增殖和凋亡激活减少， 分别。结果表明，负载Ce6的核糖体代表了用于光动力治疗鳞状细胞癌的方便制剂。与正常的皮肤成纤维细胞球体相比，Ce6核糖体的PDT效果具有特异性，并且显示出对鳞状细胞癌球体更高的细胞毒性。此外，PDT处理在鸡卵绒毛膜上生长的鳞状细胞癌异种移植物（CAM）表现出Ki-67增殖标志物的表达减少和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）染色增加，表明增殖和凋亡激活减少， 分别。结果表明，负载Ce6的核糖体代表了用于光动力治疗鳞状细胞癌的方便制剂。PDT处理在鸡的绒毛膜上生长的鳞状细胞癌异种移植物（CAM）表现出Ki-67增殖标志物的表达减少和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）染色增加，分别表明增殖减少和凋亡激活。结果表明，负载Ce6的核糖体代表了用于光动力治疗鳞状细胞癌的方便制剂。PDT处理在鸡的绒毛膜上生长的鳞状细胞癌异种移植物（CAM）表现出Ki-67增殖标志物的表达减少和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）染色增加，分别表明增殖减少和凋亡激活。结果表明，负载Ce6的核糖体代表了用于光动力治疗鳞状细胞癌的方便制剂。