Transethosome-based topical administration systems with enhanced penetration and dual actions for treating EGFR-overexpressed cutaneous squamous cell carcinoma

• Main Authors: Wang, Wenyan, Tham, Phoebe Huijun, Ding, Chendi, Huang, Ping, Li, Tingxuan, Luo, Jingjing, Xiang, Huijing, Zeng, Xiaowei, Chen, Hongzhong, Zhao, Yanli
• Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
• Format: Article
• Language: English
• Published: 2024
• Subjects: Medicine, Health and Life Sciences; Cutaneous squamous cell carcinoma; EGFR inhibitor
• Online Access: https://hdl.handle.net/10356/177932
• Institution: Nanyang Technological University

Epidermal growth factor receptor (EGFR)-overexpressing cutaneous squamous cell carcinoma (CSCC) necessitates more effective therapies due to its elevated metastasis risk compared to the conventional CSCC. While photodynamic therapy (PDT) is a promising way to treat CSCC, effectively administering photosensitizers to reach deeper skin malignancies remains a challenge. Herein, BE-TEL is reported, a transethosome formulation designed to enhance skin and cutaneous tumor permeability, for targeted treatment of EGFR-overexpressed CSCC. The formulation is co-loaded with Erlotinib (Erb), a hydrophobic EGFR inhibitor, and BODIPY (BPY), a photosensitizer. Upon skin penetration and subsequent exposure to 660 nm light, BE-TEL induces tumor cell apoptosis by reactive oxygen species (ROS) generation and EGFR pathway inhibition. ROS and Erb-induced metabolic oxidative stress by upregulating the expression of NADPH oxidase 4 (NOX4) can enhance immunogenic cell death (ICD) and promote dendritic cell maturation for tumor-specific immune response. Furthermore, the EGFR downregulation further mitigated the risk of metastasis and recurrence. In conclusion, BE-TEL's superior penetration ability together with its combined PDT and EGFR targeted approach paves the way for an efficient strategy against EGFR-overexpressed CSCC.