Tumor cell-specific retention of photosensitizers determines the outcome of photodynamic therapy for head and neck cancer

• Published in: Journal of photochemistry and photobiology. B, Biology Biology, 2022-09, Vol.234, p.112513-112513, Article 112513
• Main Authors: Tracy, Erin C., Bowman, Mary-Jo, Pandey, Ravindra K., Baumann, Heinz
• Format: Article
• Language: English
• Subjects: Binding; Cancer; Cancer cell models; Epithelial cells; Epithelium; Head & neck cancer; Lead compounds; Lesions; Patients; PDT biomarker; Pheophorbide; Photodynamic therapy; Photoreaction; Retention; Specific retention; Tumor cells; Tumor tissue analysis; Tumors; Xenografts; Xenotransplantation
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2022.112513

Pheophorbide-based photosensitizers have demonstrated tumor cell-specific retention. The lead compound 3-[1′-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) in a clinical trial for photodynamic therapy of head and neck cancer lesions indicated a complete response in 80% of patients. The question arises whether the partial response in 20% of patients is due to inefficient retention of photosensitizers by tumor cells and, if so, can the photosensitizer preference of individual cancer cases be identified prior to photodynamic therapy. This study determined the specificity of head and neck cancer cells and tumor tissues for the uptake and retention of diffusible pheophorbides differing in peripheral groups on the macrocycle that contribute to cellular binding. The relationship between photosensitizer level and light-mediated photoreaction was characterized to identify markers for predicting the effectiveness of photodynamic therapy in situ. The experimental models were stromal and epithelial cells isolated from head and neck tumor samples and integrated into monotypic tissue cultures, reconstituted three-dimensional co-cultures, and xenografts. Tumor cell-specific photosensitizer retention patterns were identified, and a procedure was developed to allow the diagnostic evaluation of HPPH binding by tumor cells in individual cancer cases. The findings of this study may assist in designing conditions for photosensitizer application and photodynamic therapy of head and neck cancer lesions optimized for each patient's case. HPPH binding to tumor cells in a cryosection of a patient's larynx sample (40X). [Display omitted] •Uptake of chlorin-based photosensitizers differs greatly among H/N tumor cells•Retention of photosensitizers is increased in dense tumor cell clusters•Biomarkers for the photoreaction predict PDT outcome•Novel technique determines HPPH-binding in tumors and facilitates optimized PDT.