Evaluation of the Targeting and Therapeutic Efficiency of Anti-EGFR Functionalised Nanoparticles in Head and Neck Cancer Cells for Use in NIR-II Optical Window.

Teklu Egnuni,Ibrahim Mirza,James R Mclaughlan,P Louise Coletta,Nicola Ingram

doi:10.3390/pharmaceutics13101651

Teklu Egnuni, Ibrahim Mirza + Show 3 more

Open Access

https://doi.org/10.3390/pharmaceutics13101651

Copy DOI

Abstract

Gold nanoparticles have been indicated for use in a diagnostic and/or therapeutic role in several cancer types. The use of gold nanorods (AuNRs) with a surface plasmon resonance (SPR) in the second near-infrared II (NIR-II) optical window promises deeper anatomical penetration through increased maximum permissible exposure and lower optical attenuation. In this study, the targeting and therapeutic efficiency of anti-epidermal growth factor receptor (EGFR)-antibody-functionalised AuNRs with an SPR at 1064 nm was evaluated in vitro. Four cell lines, KYSE-30, CAL-27, Hep-G2 and MCF-7, which either over- or under-expressed EGFR, were used once confirmed by flow cytometry and immunofluorescence. Optical microscopy demonstrated a significant difference (p < 0.0001) between targeted AuNRs (tAuNRs) and untargeted AuNRs (uAuNRs) in all four cancer cell lines. This study demonstrated that anti-EGFR functionalisation significantly increased the association of tAuNRs with each EGFR-positive cancer cell. Considering this, the MTT assay showed that photothermal therapy (PTT) significantly increased cancer cell death (>97%) in head and neck cancer cell line CAL-27 using tAuNRs but not uAuNRs, apoptosis being the major mechanism of cell death. This successful targeting and therapeutic outcome highlight the future use of tAuNRs for molecular photoacoustic imaging or tumour treatment through plasmonic photothermal therapy.

Highlights

80.54% of the total cell counts were positive for anti-epidermal growth factor receptor (EGFR) staining in KYSE-30 and CAL-27, respectively, only 5.7% and 2.3% were positive in Hep G2 and MCF-7 cells, respectively
The percentage total count and median fluorescent intensity (MFI) results imply a significantly increased EGFR expression level in KYSE-30 and CAL-27 compared with Hep G2 and MCF-7 cells
(% parent), mean and median fluorescence intensity of both isotype and anti-EGFR antibodies in 4 different cancer cell types. (C) Immunofluorescence staining of these four cancer cell lines using anti-EGFR and isotype antibodies showed a high expression of EGFR in KYSE-30 and CAL-27 compared with Hep G2 and MCF-7 cancer cell lines

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and contributes to 90% of all head and neck cancers [1]. Tobacco and human papilloma virus (HPV) infection are major known risk factors of HNSCC [2]. The current standard of therapy for HNSCC patients has an overall 5-year survival rate of 35–54% [3], these conventional therapies suffer from debilitating side effects, such as temporary or permanent loss of speech, loss of hearing, chewing and/or swallowing, fatigue, hair loss, sore throat following damage to healthy tissues of the throat, salivary gland, thyroid gland and lymph nodes [4,5,6,7]. The overall patient survival depends on the stage and molecular subtypes of the HNSCC. Chung et al [8] and Walter et al [9]

Methods

Results

Conclusion