PUBLICATION
Targeting Radiation Resistance in Oesophageal Adenocarcinoma with Pyrazinib-Functionalised Gold Nanoparticles
- Authors
- Marcone, S., Spadavecchia, J., Khan, M., Vella, G., O'Connell, F., Pendino, M., Menon, M., Donohoe, C., Narayanasamy, R., Reynolds, J.V., Maher, S.G., Lynam-Lennon, N., Kennedy, B., Prina-Mello, A., O'Sullivan, J.
- ID
- ZDB-PUB-241218-2
- Date
- 2024
- Source
- Cancers 16(23): (Journal)
- Registered Authors
- Kennedy, Breandan N.
- Keywords
- angiogenesis, gold nanoparticles, metabolism, radioresistance, targeted delivery
- MeSH Terms
- none
- PubMed
- 39682192 Full text @ Cancers
Citation
Marcone, S., Spadavecchia, J., Khan, M., Vella, G., O'Connell, F., Pendino, M., Menon, M., Donohoe, C., Narayanasamy, R., Reynolds, J.V., Maher, S.G., Lynam-Lennon, N., Kennedy, B., Prina-Mello, A., O'Sullivan, J. (2024) Targeting Radiation Resistance in Oesophageal Adenocarcinoma with Pyrazinib-Functionalised Gold Nanoparticles. Cancers. 16(23):.
Abstract
Background/Objectives: Only 20-30% of oesophageal adenocarcinoma (OAC) patients achieve a complete response to neoadjuvant chemo-radiotherapy for locally advanced tumours. Enhancing the response to radiation therapy is critical for improving outcomes in this aggressive cancer. Pyrazinib (P3) is a promising compound with radiosensitizing, anti-angiogenic, anti-inflammatory, and anti-metabolic properties. However, its limited solubility and bioavailability have hindered its therapeutic potential.
Methods To overcome these limitations, pyrazinib was conjugated with gold nanoparticles (AuNP-P3), creating a novel formulation designed to enhance solubility, maintain bioactivity, and enable targeted delivery to tumour sites.
Results In an isogenic model of OAC radioresistance, AuNP-P3 significantly reduced the surviving fraction following irradiation, demonstrating its radiosensitizing properties. It also reduced mitochondrial metabolism and modulated the secretion of inflammatory mediators in both in vitro models of OAC radioresistance and human ex vivo OAC tumour explants. Furthermore, AuNP-P3 exhibited potent anti-angiogenic activity, significantly inhibiting blood vessel formation in vivo using zebrafish embryo models.
Conclusions These results collectively confirm that P3, in its conjugated formulation with gold nanoparticles, retains its therapeutic properties, highlighting the potential of AuNP-P3 as a novel therapeutic radiosensitizer for oesophageal adenocarcinoma and supporting its further development for clinical applications.
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Human Disease / Model
Sequence Targeting Reagents
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