Hyaluronan-mediated ferric oxide nanoparticles causes apoptosis of CD44 expressing head and neck squamous cell carcinoma cells

Anthony Bogedin,Jason Gorski,Ranjeeta Thapa

doi:10.14319/ijcto.42.4

Anthony Bogedin, Jason Gorski + Show 1 more

Open Access

https://doi.org/10.14319/ijcto.42.4

Copy DOI

Abstract

Purpose: To eliminate CD44, a putative cancer stem cell (CSC) marker, overexpressing head and neck squamous cell carcinoma (HNSCC) cells by using hyaluronan-conjugated, dextran-coated super paramagnetic iron oxide nanoparticles (HA-DESPIONs), in conjunction with induced heat produced by exposure to an alternating magnetic field (AMF). Methods: An AMF generator was constructed by means of a solenoid coil and an impedance circuit driven by a power amplifier. A signal generator produced a small sinusoidal signal of 130 kHz that was then amplified to 9 A (peak to peak value) to generate an AMF of approximately 10 kA/m (12.6 mT) at the center of a coil. The heat generating effect of the AMF generator was tested via several kinetic and dose-dependent bulk heating experiments by exposing readily available magnetic nanoparticles to AMF. For elimination of CD44 population, UT-SCC-14 cells were exposed to either targeted HA-DESPIONs or non-targeted DESPIONs at a concentration 200 μg/ml and exposed to AMF for 30 minutes. Cells were processed after 24 hours for flow cytometry based analysis of apoptosis. Results: Magnetic nanoparticles caused a concentration-dependent bulk heating effect in response to AMF resulting in a significant temperature rise. Following the exposure to AMF, non-conjugated DESPIONs were unable to induce targeted hyperthermia and hence had no effect on CD44 cell death in HNSCC cells. However, there was a significant cell death in the CD44 population treated with HA-DESPIONs and exposed to AMF. This effect was only obeserved when the magnetic field was turned on. Conclusion: Bulk heating experiments concluded that a simple AMF generator was able to activate magnetic nanoparticles and flow cytometry demonstrated that HA- DESPIONs were able to cause apoptosis in UT-SCC-14 cells that express CD44.This may be a promising strategy to specifically target cancer stem cells (CSCs) for the treatment of HNSCC.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is the most frequent malignant form of head and neck cancer originating from the mucosal lining of the upper aerodigestive tract
3.1 Bulk heating results The initial studies verified that the alternating magnetic field (AMF) generator was capable of activating the magnetic nanoparticles to produce significant increases in temperature
In terms of the in vitro studies, our results suggested that HA-DESPIONs bind to CD44 expressing cells but required 24 hours of incubation to result in a significant amount of apoptotic CD44 cell death as hyperthermia treatments performed immediately after the addition of nanoparticle solution had no significant difference in apoptotic cell death

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the most frequent malignant form of head and neck cancer originating from the mucosal lining of the upper aerodigestive tract.

Methods

Results

Discussion

Conclusion