A major challenge to detect and treat chronic inflammatory diseases such as cancer and atherosclerosis (i.e. hardening of the arteries due to fat accumulation) is to effectively deliver contrast agents and therapeutics into the pathological tissues whilst avoiding off-target binding and consequent cytotoxic effects. Our team focuses on developing tools and strategies to target the microenvironment of cancers (i.e. breast carcinoma, insulinoma and hepatocellular carcinoma) and atherosclerotic plaques for imaging and therapy.
We have recently characterised a number of small molecules (i.e. peptides) that specifically bind to the abnormal cellular and non-cellular components in cancers and atherosclerotic lesions, including blood vessels, macrophages and extracellular matrix. These tumour and plaque –specific peptides can then be used as a drug delivery agent into the pathological tissues.
Using chemical coupling and bioengineering approaches, we are now developing imaging contrast agents and therapeutics fused with these targeting peptides for in vivo applications in pre-clinical models of cancers and atherosclerosis.
Figure 1 (below): Peptide homing (green) in vivo in tumours and plaques. Source: Unpublished
Improved diagnostic imaging for detecting cancers and atherosclerosis in vivo
We have developed multifunctional nanoparticle-based system to carry contrast agents to image tumours and plaques using advanced imaging instrument including microPET/CT, MRI and confocal imaging. Importantly, these reagents are fused to the homing peptides to improve binding and accumulation deep in tumours and plaques.
Our goal is to be able to detect the developing tumours and atherosclerotic lesions at their earliest form as well as at the advanced chronic stages that are known to cause severe complications.
Figure 2 (below): PET imaging of atherosclerosis in vivo. Source: Hamzah et al. PNAS, 2011
Targeted therapy to destroy pathological lesions and reverse inflammation in cancers and atherosclerosis
Our team explores two fundamentally different therapeutic interventions which involve targeting tumours and plaques to: i) destroy selective cellular components that contribute to the progression of cancers and atherosclerosis, and ii) re-program the diseased-promoting microenvironment by reversing specific inflammatory condition in the pathological tissues.
We engineered several classes of cell-killing agents and inflammatory mediators fused with tumour and plaque targeting peptides for effective delivery. We aim to monitor the drug penetration in tumours and plaques (by imaging) and evaluate the implications of these therapeutic strategies on cancer and plaque progression.
Figure 3 (below): Immune cell infiltration in tumours in response to targeted delivery. Source: Unpublished