Evaluating the cytotoxicity of Ge-Sb-Se chalcogenide glass optical fibres on 3T3 mouse fibroblasts.

David Mabwa,Colin A Scotchford,Harriet Parnell,David Furniss,Teo Kubiena,Angela B Seddon,Rong Su,Richard Leach,Zhuoqi Tang,Trevor M Benson

doi:10.1039/d0ra00353k

David Mabwa, Colin A Scotchford + Show 8 more

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https://doi.org/10.1039/d0ra00353k

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Abstract

In vivo cancer detection based on the mid-infrared molecular fingerprint of tissue is promising for the fast diagnosis and treatment of suspected cancer patients. Few materials are mid-infrared transmissive, even fewer, which can be converted into functional, low-loss optical fibres for in vivo non-invasive testing. Chalcogenide-based glass optical fibres are, however, one of the few. These glasses are transmissive in the mid-infrared and are currently under development for use in molecular sensing devices. The cytotoxicity of these materials is however unknown. The cytotoxicity of Ge–Sb–Se chalcogenide optical glass fibres on 3T3 mouse fibroblast cells is here investigated. Fibres exposed to four different pre-treatment conditions are used: as-drawn (AD), propylamine-etched (PE), oxidised-and-washed (OW) and oxidised (Ox). To achieve the latter two conditions, fibres are treated with H2O2(aqueous (aq.)) and dried to produce a surface oxide layer; this is either washed off (OW) or left on the glass surface (Ox). Cellular response is investigated via 3 day elution and 14 day direct contact trials. The concentration of the metalloids (Ge, Sb and Se) in each leachate was measured via inductively coupled plasma mass spectrometry. Cell viability is assessed using the neutral red assay and scanning electron microscopy. The concentration of Ge, Sb and Se ions after a 3 day dissolution was as follows. In AD leachates, Ge: 0.40 mg L−1, Sb: 0.17 mg L−1, and Se: 0.06 mg L−1. In PE leachates, Ge: 0.22 mg L−1, Sb: 0.15 mg L−1, and Se: 0.02 mg L−1. In Ox leachates, Ge: 823.8 mg L−1, Sb: 2586.6 mg L−1, and Se: 3750 mg L−1. Direct contact trials show confluent cell layers on AD, PE and OW fibres after 14 days, while no cells are observed on the Ox surfaces. A >50% cell viability is observed in AD, PE and OW eluates after 3 days, when compared with Ox eluates (<10% cell viability). Toxicity in Ox is attributed to the notable pH change, from neutral pH 7.49 to acidic pH 2.44, that takes place on dissolution of the surface oxide layer in the growth media. We conclude, as-prepared Ge–Sb–Se glasses are cytocompatible and toxicity arises when an oxide layer is forced to develop on the glass surface.

Highlights

Over 100 different types of cancers occur in humans, and only four: breast, colon, prostate, and lung, are responsible for more than half of all diagnoses, with a comparable proportion of deaths
Fibres were initially cleaved into 5 mm and 10 mm long lengths, subjected to one of three pre-treatment conditions. These were, submersion in propylamine for 0.5 h (PE); submersion in H2O2(aq.) for 10, 30 and 60 min and subsequent drying in ambient conditions for 12 h, to allow the build-up of a glass oxide layer (O10, O30, O60, respectively) and submersion in H2O2(aq.) for 60 min and subsequent drying as previously described and triplicate washing in both acetone and isopropanol to remove the oxide layer (OW) drying in ambient conditions via evaporation
In AD, Ge and Sb concentrations increase by 222% and 159%, respectively, from D1 (Ge: 0.31 mg LÀ1, Sb: 0.19) to D14 (Ge: 1.02 mg LÀ1, Sb: 0.50 mg LÀ1), while Se is seen to decrease by 61.7% from D1 (Se: 0.12 mg LÀ1) to D14 (Se: 0.045 mg LÀ1)

Summary

Introduction

Over 100 different types of cancers occur in humans, and only four: breast, colon, prostate, and lung, are responsible for more than half of all diagnoses, with a comparable proportion of deaths. It is currently limited to only imaging excised tissue This is due to traditionally weak MIR light blackbody sources and the lack of optical bre that transmits sufficiently into the MIR spectral region.[6] The latter limitation has since been resolved since the advent of chalcogenide-based optical bres, derived from the chalcogen elements of group 16 in the periodic table (S, Se and Te – excluding O).[7] With the aim of providing point-of-care testing, in previous work, we developed low optical loss Ge20Sb10Se70 atomic (at) % glass optical bres capable of transmitting MIR light from 2.5 mm–13 mm.[8] This glass system opens the possibility of utilising MIR hyperspectral imaging for the diagnosis of cancerous tissue, in vivo, through its incorporation into endoscopic probes.[9]

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