The synthesis and application of iron oxide nanoparticles for targeted imaging using MRI
Creators: name: Arora, Jyoti
Publisher: name: RMIT University
Year: 2024

description: The work presented in this PhD describes the use of highly magnetic iron oxide silica nanoparticles conjugated to herceptin for the targeted detection of human epidermal growth factor receptor 2 (HER2) positive breast cancer using magnetic resonance imaging (MRI).<br><br>A promising use of nanoparticles is in medical imaging where iron oxide nanoparticles are increasingly being utilised in MRI as contrast agents for targeted imaging. Iron oxide particles have previously been used as contrast agents for imaging liver, spleen and gastrointestinal lumen in MRI. With advancements in nanoparticle technology, iron oxide nanoparticles that are less than 100 nm in diameter have been able to be synthesised which are capable of imaging specific diseases targeted with a biomarker. This advancement is a crucial development for medical imaging as it allows targeted imaging to be possible with MRI.<br><br>An application of iron oxide nanoparticles for targeted imaging in MRI is in breast cancers that overexpress HER2 receptors which are associated with poor prognosis. A treatment option for HER2 positive tumours is Herceptin® (herceptin) therapy, which is known to eventually cause a reduction in tumour size. Although the response rates to herceptin therapy regimes are high, it is documented that patients acquire resistance after several months. The primary mechanism of herceptin resistance is unknown and there are varieties of pathways that have been proposed. Although there are research efforts to understand the myriad of molecular mechanisms related to herceptin resistance, it is also equally important to identify the patients who may be resistant to herceptin based therapy.<br><br>A tool that can be used is to image HER2 positive breast tumours and potentially identify these patients using MRI and iron oxide nanoparticles conjugated to herceptin. There have been previous studies demonstrating that HER2 positive breast tumours can be targeted using iron oxide nanoparticles in MRI. Unfortunately, these studies do not meet all of the characteristics that are required to achieve targeted imaging in MRI. Due to this, iron oxide nanoparticles for targeted imaging in MRI have been limited in their translational capability to the clinic.<br><br>Therefore, the aim of this PhD was to synthesise iron oxide nanoparticles for targeting HER2 positive tumours in vitro and in vivo. The main finding of this study was that iron oxide nanoparticles coated in silica can be used to detect HER2 positive breast cancers in vivo using MRI. The iron oxide silica nanoparticles produced presented with highly magnetic properties, superior to commercially available products, and were able to produce MRI contrast. The nanoparticles were also found to be non-toxic, biocompatible, stable and were easily conjugated to herceptin. The results from the in vitro and in vivo assessment of these iron oxide silica herceptin nanoparticles, demonstrated MRI contrast relative to HER2 expression levels in three human breast cancer cell lines and HER2 positive breast tumours.<br><br>Overall, the findings of this study demonstrated that the iron oxide silica herceptin nanoparticles targeted HER2 positive tumours suggesting they have all of the basic characteristics required for potential translation into the clinical setting.