title: Novel delivery of Chlorin e6 using anti-EGFR antibody tagged virosomes for fluorescence diagnosis of oral cancer in a hamster cheek pouch model.
abstract: OBJECTIVE
  Overexpression of epidermal growth factor receptor (EGFR) is observed in oral squamous cell carcinoma (OSCC) and is associated with increased proliferation, metastasis and therapeutic resistance. We aim to develop a novel drug delivery system comprised of a photosensitizer Chlorin e6 (Ce6) that is encapsulated in a viral envelope and tagged with anti-EGFR antibody to target OSCC.
  
  
  METHODS
  Ce6 was encapsulated in both virosomes (Ce6-Vir) and virosomes tagged with anti-EGFR antibody (Ce6-Vir-EGFR'). In vitro studies were conducted to assess the cellular uptake and bioavailability of the photosensitizer in OSCC cells. Ce6 alone or in constructs was then administered in a hamster cheek pouch model and fluorescence imaging and spectroscopy was performed.
  
  
  RESULTS
  In vitro results showed that the uptake of Ce6-Vir-EGFR' was lower than that for Ce6-Vir and Ce6 possibly due to its large size. Nevertheless, in vivo results showed significant tumor specificity of Ce6-Vir-EGFR' compared to Ce6. The tumor to normal mucosa ratio showed that Ce6-Vir-EGFR' can successfully target OSCC lesions and therefore shows potential for use in fluorescence diagnosis of OSCC.
  
  
  CONCLUSIONS
  Both the virosome-Ce6 constructs were internalized by OSCC cells and successfully used for fluorescence imaging. Tagging with anti-EGFR antibody further improved the targeting ability toward OSCC.
authors.affiliation: Division of Medical Sciences, National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore.
authors.forename: Kar Perng
authors.initials: KP
authors.lastname: Low
authors.affiliation: Division of Medical Sciences, National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore.
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Bhuvaneswari
authors.affiliation: Division of Medical Sciences, National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore. Electronic address: nmstsp@nccs.com.sg.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Thong
authors.affiliation: Office of Research, Duke-NUS Graduate Medical School, 8 College Road, 169857, Singapore.
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Bunte
authors.affiliation: Division of Medical Sciences, National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore; Office of Research, Duke-NUS Graduate Medical School, 8 College Road, 169857, Singapore.
authors.forename: Khee Chee
authors.initials: KC
authors.lastname: Soo
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002273:Carcinogens; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002610:Cheek; D002735:Chlorophyllides; D006224:Cricetinae; D066246:ErbB Receptors / Q000276:immunology*; D005453:Fluorescence; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D009061:Mouth Mucosa / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D061848:Optical Imaging; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D011166:Porphyrins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D022701:Virosomes
chemical_list: D000911:Antibodies, Monoclonal; D002273:Carcinogens; D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; D022701:Virosomes; D015127:9,10-Dimethyl-1,2-benzanthracene; C062985:phytochlorin; D066246:ErbB Receptors
keywords: 7,12-Dimethylbenz[a]anthracene (PubChem CID: 6001); Anti-EGFR antibody; Chlorin e6; Chlorin e6 (PubChem CID: 5357355); Dimethyl sulfoxide (PubChem CID: 679); Dormicum (PubChem CID: 4192); Eosin (PubChem CID: 11048); Fluorescence diagnosis; Hamster cheek pouch model; Hematoxylin (PubChem CID: 320930); Hypnorm (PubChem CID: 171220); Oral squamous cell carcinoma; Virosomes