ECM Depletion Is Required to Improve the Intratumoral Uptake of Iron Oxide Nanoparticles in Poorly Perfused Hepatocellular Carcinoma.

Improving tumor access for drug delivery is challenging, particularly in poorly perfused tumors. The availability of functional tumor blood vessels for systemic access is vital to allow drugs or imaging agents to accumulate in the tumor parenchyma. We subjected mice engineered to develop hepatocellular carcinoma (HCC), to treatment with tumor necrosis factor alpha (TNFα) conjugated to a CSG peptide (CSGRRSSKC).

Enhanced Detection of Desmoplasia by Targeted Delivery of Iron Oxide Nanoparticles to the Tumour-Specific Extracellular Matrix.

Diagnostic imaging of aggressive cancer with a high stroma content may benefit from the use of imaging contrast agents targeted with peptides that have high binding affinity to the extracellular matrix (ECM). In this study, we report the use of superparamagnetic iron-oxide nanoparticles (IO-NP) conjugated to a nonapeptide, CSGRRSSKC (CSG), which specifically binds to the laminin-nidogen-1 complex in tumours. We show that CSG-IO-NP accumulate in tumours, predominantly in the tumour ECM, following intravenous injection into a murine model of pancreatic neuroendocrine tumour (PNET).

Immune-mediated ECM depletion improves tumour perfusion and payload delivery.

High extracellular matrix (ECM) content in solid cancers impairs tumour perfusion and thus access of imaging and therapeutic agents. We have devised a new approach to degrade tumour ECM, which improves uptake of circulating compounds. We target the immune-modulating cytokine, tumour necrosis factor alpha (TNFα), to tumours using a newly discovered peptide ligand referred to as CSG.

Ultrahigh-resolution optical coherence elastography through a micro-endoscope: towards imaging of cellular-scale mechanics.

In this paper, we describe a technique capable of visualizing mechanical properties at the cellular scale deep in living tissue, by incorporating a gradient-index (GRIN)-lens micro-endoscope into an ultrahigh-resolution optical coherence elastography system. The optical system, after the endoscope, has a lateral resolution of 1.6 m and an axial resolution of 2.