Photodynamic therapeutic effect of indocyanine green entrapped in polymeric nanoparticles and their anti-EGFR-conjugate in skin cancer in CD1 mice

• Published in: Photodiagnosis and photodynamic therapy 2013-12, Vol.10 (4), p.446-459
• Main Authors: Gamal-Eldeen, Amira M., M.Sc, El-Daly, Sherien M, Borai, Ibrahim H, Wafay, Hanaa A, Abdel-Ghaffar, Abdel-Rahman B
• Format: Article
• Language: English
• Subjects: 5-LOX; Animals; Antibodies, Monoclonal - therapeutic use; Apoptosis; Caspase-3; COX-2; Female; Hematology, Oncology and Palliative Medicine; Indocyanine green; Indocyanine Green - administration & dosage; Internal Medicine; Mice; Nanocapsules - chemistry; Nanocapsules - therapeutic use; Nanocapsules - ultrastructure; Nitric oxide; PCNA; PEBBLE; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - therapeutic use; Polymeric nanoparticles; Polymers - chemistry; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - metabolism; Siloxanes - chemistry; Skin cancer; Skin Neoplasms - drug therapy; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; TNF-α; Treatment Outcome; VEGF
• ISSN: 1572-1000; 1873-1597
• DOI: 10.1016/j.pdpdt.2013.03.013

Summary Background Indocyanine green (ICG) is a promising photosensitive agent for photodynamic therapy (PDT) of tumors. Encapsulating ICG dye in polymeric nanoparticles based on PEBBLE technology forming (ICG-PEBBLE) could improve the aqueous stability of the entrapped ICG molecules. The study objective is to investigate the PDT effect of free ICG-PEBBLE and its Anti-EGFR conjugate. Methods Skin squamous cell carcinoma was induced in CD1 mice by dimethylbenzanthracene (DMBA) and 12- O -tetradecanoyl-phorbol-13-acetate (TPA) followed by a PDT protocol for four weeks. Results PDT using ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR decreased skin tumor sizes. Our findings revealed that the inflammatory mediators tumor necrosis factor (TNF-α), nitric oxide (NO), cycloxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), the angiogenic mediator vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) were decreased, while apoptosis, caspase-3 and histone acetylation were induced in tumor bearing groups after PDT using both of ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR. Conclusion The present study indicated the effectiveness of PDT using ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR as an inhibitor modality for tumor size, apoptosis, angiogenesis and tumor inflammation. The conjugating of ICG-PEBBLE to anti-EGFR was found to be more effective in inhibiting VEGF and in increasing caspase-3 compared to free ICG-PEBBLE, but there were no other preferential PDT efficacy.