Publications

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health challenge. Currently treatment of drug-sensitive TB, involves a six-month regimen consisting of a combination of four anti-TB drugs, with drug-resistant TB requiring over two years of treatment and additional drugs. As toxicity of anti-TB drugs often leads to poor compliance, disease relapse and the emergence of drug-resistant strains, new strategies to reduce drug toxicity and shorten treatment duration are critical. We report nanocarrier-based drug delivery systems targeting macrophages, which primarily support replication and survival of Mtb. We demonstrate that antibiotic-containing nanocarriers efficiently accumulated in macrophages without causing toxicity. Encapsulated RIF showed enhanced efficacy against both BCG and Mtb in primary macrophages. Biodistribution studies in mice revealed that the nanoparticles have extended circulation time and do not induce toxicity. In addition, the encapsulated RIF showed better targeting of mycobacteria when compared to free RIF in a murine model of mycobacterial infection. Such an enhanced bacterial killing using mannose-functionalised nanocarriers loaded with the key anti-TB drug rifampicin offers excellent potential for TB therapy.

Vadim's magnum opus now online as a preprint. 7 years after the initial preprint, 2 PhD students working on it. A coolaboration with David Rand and also including input Francis Lévi and with data from George Bjarnasson and Tami Martino.

We show in over 1200 patients that TimeTeller predicted functional tumour clocks have a negative effect on 10-year survival in breast cancer patients. Also, the tumour clocks are "off" compared to wall clock time, which we speculate might be a feature of tumour evading detection by the patients immune system.

Ed Lant's paper on cool molecular helicopters that also fluoresc entitled: "In Situ Lipid Interactions of an Anticancer Metal Complex". A big collaboration with Peter Sadler's lab and collaborators from Diamond (Maria Harkiolaki) and others.

In this paper, Ed uses an integrated multimodal imaging workflow of cryogenic super-resolution fluorescence microscopy and soft X-ray tomography, Orbitrap secondary ion mass spectrometry, and inductively coupled mass spectrometry to reveal unexpected targeting of a half-sandwich cyclopentadienyl Rh(III) phenylazopyridine anticancer complex to cellular lipid membranes and lipid droplets.

The complex accumulates in plasma membranes with a surprisingly intense switch-on luminescence in living cancer cells, drives remodelling of lipid droplet architecture, and penetrates deeply into lipid-rich tissue environments. DFT modelling shows strong supramolecular interactions between the complex and glycerophosphorylcholine lipids.