Nanobody-targeted photodynamic therapy for the treatment of feline oral carcinoma: a step towards translation to the veterinary clinic.

Irati Beltrán Hernández,Erik Teske,Jan W. Hesselink,Jan A. Mol,Alessia Di Maggio,Wim E. Hennink,Guillaume C.M. Grinwis,Paul M.P. van Bergen en Henegouwen,Sebastiaan A. van Nimwegen,Sabrina Oliveira

doi:10.1515/nanoph-2021-0195

Irati Beltrán Hernández, Erik Teske + Show 8 more

Open Access

https://doi.org/10.1515/nanoph-2021-0195

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Journal: Nanophotonics	Publication Date: Aug 2, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: Utrecht University

Abstract

Nanobody-targeted photodynamic therapy (NB-PDT) has been developed as a potent and tumor-selective treatment, using nanobodies (NBs) to deliver a photosensitizer (PS) specifically to cancer cells. Upon local light application, reactive oxygen species are formed and consequent cell death occurs. NB-PDT has preclinically shown evident success and we next aim to treat cats with oral squamous cell carcinoma (OSCC), which has very limited therapeutic options and is regarded as a natural model of human head and neck SCC. Immunohistochemistry of feline OSCC tissue confirmed that the epidermal growth factor receptor (EGFR) is a relevant target with expression in cancer cells and not in the surrounding stroma. Three feline OSCC cell lines were employed together with a well-characterized human cancer cell line (HeLa), all with similar EGFR expression, and a low EGFR-expressing human cell line (MCF7), mirroring the EGFR expression level in the surrounding mucosal stroma. NBA was identified as a NB binding human and feline EGFR with comparable high affinity. This NB was developed into NiBh, a NB-PS conjugate with high PS payload able to effectively kill feline OSCC and HeLa cell lines, after illumination. Importantly, the specificity of NB-PDT was confirmed in co-cultures where only the feline OSCC cells were killed while surrounding MCF7 cells were unaffected. Altogether, NiBh can be used for NB-PDT to treat feline OSCC and further advance NB-PDT towards the human clinic.

Highlights

Nanobody-targeted photodynamic therapy (NB-PDT) has been developed since 2014 as a highly tumorselective treatment [1,2,3,4,5,6,7,8]
As epidermal growth factor receptor (EGFR) has been described to be overexpressed in feline oral squamous cell carcinoma (OSCC) [22, 23], immunohistochemistry was performed on 10 cases of feline OSCC to investigate the expression of this protein in neoplastic cells and to elucidate its presence in cells of the surrounding normal oral mucosa
Membranous EGFR expression was detected in the normal adjacent oral epithelium, more prominently in the basal cell layer and decreasing towards the outer, more differentiated epithelial layers (Figure 1(a), left)

Summary

Introduction

NB-PDT has been developed since 2014 as a highly tumorselective treatment [1,2,3,4,5,6,7,8]. Photosensitizers are light-activatable compounds that, upon accumulation in the tumor, can be excited by light of a particular wavelength locally applied at the tumor site, leading to the formation of reactive oxygen species and consequent cell death [10, 11]. In this respect, two levels of specificity, i.e. tumor targeting via NBs and local PS activation, make it possible to effectively kill cancer cells, while sparing surrounding healthy tissue.

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