title: Photodynamic therapeutic effect of indocyanine green entrapped in polymeric nanoparticles and their anti-EGFR-conjugate in skin cancer in CD1 mice.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cancer Biology Laboratory, Center of Excellence for Advanced Sciences, National Research Center, Cairo, Egypt; Department of Biochemistry, National Research Center, Cairo, Egypt. Electronic address: aeldeen7@yahoo.com.
authors.forename: Amira M
authors.initials: AM
authors.lastname: Gamal-Eldeen
authors.forename: Sherien M
authors.initials: SM
authors.lastname: El-Daly
authors.forename: Ibrahim H
authors.initials: IH
authors.lastname: Borai
authors.forename: Hanaa A
authors.initials: HA
authors.lastname: Wafay
authors.forename: Abdel-Rahman B
authors.initials: AR
authors.lastname: Abdel-Ghaffar
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D007208:Indocyanine Green / Q000008:administration & dosage*; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry / Q000627:therapeutic use* / Q000648:ultrastructure; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011108:Polymers / Q000737:chemistry; D012833:Siloxanes / Q000737:chemistry; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D053769:Nanocapsules; D017319:Photosensitizing Agents; D011108:Polymers; D012833:Siloxanes; C510784:ormosil; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D007208:Indocyanine Green
keywords: 5-LOX; Apoptosis; COX-2; Caspase-3; Indocyanine green; Nitric oxide; PCNA; PEBBLE; Photodynamic therapy; Polymeric nanoparticles; Skin cancer; TNF-α; VEGF