| Autor: |
Nasr S; Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, D-89081 Ulm, Germany.; Department of Chemistry, School of Sciences and Engineering, The American University in Cairo (AUC), Cairo 11835, Egypt., Rady M; Pharmaceutical Technology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City 11865, Egypt., Sebak A; Pharmaceutical Technology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City 11865, Egypt., Gomaa I; Biochemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), 6th of October City 12573, Egypt., Fayad W; Drug Bioassay-Cell Culture Laboratory, Pharmacognosy Department, National Research Centre, Dokki, Giza 12622, Egypt., Gaafary ME; Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, D-89081 Ulm, Germany.; Department of Pharmacognosy, College of Pharmacy, Cairo University, Cairo 11562, Egypt., Abdel-Kader M; National Institute of Laser Enhanced Sciences (NILES), Cairo University (CU), Giza 12511, Egypt., Syrovets T; Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, D-89081 Ulm, Germany., Simmet T; Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, D-89081 Ulm, Germany. |
| Abstrakt: |
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. |
