Novel delivery of Chlorin e6 using anti-EGFR antibody tagged virosomes for fluorescence diagnosis of oral cancer in a hamster cheek pouch model

Abstract

Purpose: 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.

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.