Chemical Science Blog

Researchers in Australia have devised a new way to test how well drugs penetrate the low-oxygen core of solid tumours. ‘Hypoxic’ regions of tumours are notoriously difficult to target with drugs and the new work could help in the development of new compounds that can effectively reach these areas and efficiently kill the cells.

Tumours often grow faster than the blood vessels that supply them, and parts of the tumour therefore become starved of oxygen and grow slowly. This makes it difficult for drugs carried in the blood to reach these areas; furthermore many drugs rely on the rapid proliferation of cancer cells, so slowly growing ones are less susceptible.

One approach has been to develop ‘prodrugs’, which become toxic to the cell only upon entering the low-oxygen environment. Some of these are based upon cobalt(III) attached to a toxic ligand. In a hypoxic environment the cobalt is reduced to cobalt(II) and the ligand is released. However, there are currently no reliable ways either to visualise the hypoxic region of a tumour or to measure penetration of the drugs.

Now, Byung Kim, Trevor Hambley and Nicole Bryce at the University of Sydney have developed a three-dimensional model of a solid tumour with a hypoxic core that allows both the hypoxic region to be highlighted and the extent of penetration of prodrugs to be measured.

An assay that combines enzymatic reactions with a fluorescent sensor could help discover new Alzheimer’s disease drugs. 

Acetylcholinesterase is an enzyme involved in the development of Alzheimer’s disease. Werner Nau and Yu Liu and their teams hope that their tandem assay could be used to search for new acetylcholinesterase inhibitors as potential drugs.

The simple, fluorescence based, tandem assay can measure micromolar concentrations of choline and acetylcholine or screen for enzyme inhibitors. The change in fluorescence is easy to detect, making the assay suitable for large scale screening. 

Reference:
Operational calixarene-based fluorescent sensing systems for choline and acetylcholine and their application to enzymatic reactions
D-S Guo, V D Uzunova, X Su, Y Liu and W M Nau, Chem. Sci., 2011, DOI: 10.1039/c1sc00231g

Nanoparticle probes for imaging cells can now be made more simply and quickly thanks to a new method reported by Chinese chemists. 

Gold nanoparticles have been widely used for bio-imaging but they need to be coated, commonly in silica, to protect them and stop them aggregating. The conventional method for silica coating is time-consuming but the team say they’ve overcome this tedious process by using an organosilica source. The resulting organosilica shell has –SH and –OH groups inside it, making it easy to functionalise with fluorescent dyes or biomolecules. 

By modifying the gold core with Raman reporters and the organosilica shell with a fluorophore, the group produced nanoparticles with three modalities of imaging – Rayleigh scattering, fluorescence and surface enhanced Raman scattering.

Reference:
Au@organosilica multifunctional nanoparticles for the multimodal imaging
Y Cui, X-S Zheng, B Ren, R Wang, J Zhang, N-S Xia and Z-Q Tian, Chem. Sci., 2011, DOI: 10.1039/c1sc00242b