The tumour microenvironment regulates tumour progression and the spread of cancer in the body. Targeting the stromal cells that surround cancer cells could, therefore, improve the effectiveness of existing cancer treatments. Here, we show that magnetic nanoparticle clusters encapsulated inside a liposome can, under the influence of an external magnet, target both the tumour and its microenvironment. We use the outstanding T2 contrast properties (r2=573-1,286 s(-1) mM(-1)) of these ferri-liposomes, which are ∼95 nm in diameter, to non-invasively monitor drug delivery in vivo. We also visualize the targeting of the tumour microenvironment by the drug-loaded ferri-liposomes and the uptake of a model probe by cells. Furthermore, we used the ferri-liposomes to deliver a cathepsin protease inhibitor to a mammary tumour and its microenvironment in a mouse, which substantially reduced the size of the tumour compared with systemic delivery of the same drug.

Glucose is a major source of energy for most living organisms and its aberrant uptake is linked to many pathological conditions. However, our understanding of disease-associated glucose flux is limited due to the lack of robust tools. To date, positron emission tomography (PET) imaging remains the gold standard for measuring glucose uptake, and no optical tools exist for non-invasive longitudinal imaging of this important metabolite in in vivo settings. Here we report the development of a novel bioluminescent glucose uptake probe (BiGluc) for real-time, non-invasive longitudinal imaging of glucose absorption both in vitro and in vivo. In addition, we demonstrate that the sensitivity of our method is comparable with commonly used 18F-FDG-PET tracers and validate BiGluc as a tool for the identification of novel glucose transport inhibitors. The new imaging reagent enables a wide range of applications in the field of metabolism and drug development.

Background:The lack of cysteine cathepsin inhibitor, stefin B (cystatin B), results in progressive myoclonus epilepsy, type 1. Results: Stefin B deficiency in macrophages resulted in increased inflammasome activation. Conclusion: Stefin B-deficient mice are significantly more sensitive to e LPS-induced sepsis due to increased caspase-11 expression and mitochondrial damage. Significance: Stefin B has an important role in limiting the inflammatory response during LPS-induced sepsis.