Finger sweat analysis enables short interval metabolic biomonitoring in humans.

Metabolic biomonitoring in humans is typically based on the sampling of blood, plasma or urine. Although established in the clinical routine, these sampling procedures are often associated with a variety of compliance issues, which are impeding time-course studies. Here, we show that the metabolic profiling of the minute amounts of sweat sampled from fingertips addresses this challenge. Sweat sampling from fingertips is non-invasive, robust and can be accomplished repeatedly by untrained personnel. The sweat matrix represents a rich source for metabolic phenotyping. We confirm the feasibility of short interval sampling of sweat from the fingertips in time-course studies involving the consumption of coffee or the ingestion of a caffeine capsule after a fasting interval, in which we successfully monitor all known caffeine metabolites as well as endogenous metabolic responses. Fluctuations in the rate of sweat production are accounted for by mathematical modelling to reveal individual rates of caffeine uptake, metabolism and clearance. To conclude, metabotyping using sweat from fingertips combined with mathematical network modelling shows promise for broad applications in precision medicine by enabling the assessment of dynamic metabolic patterns, which may overcome the limitations of purely compositional biomarkers.

Interfering with Metabolic Profile of Triple-Negative Breast Cancers Using Rationally Designed Metformin Prodrugs.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by an aberrant metabolic phenotype with high metastatic capacity, resulting in poor patient prognoses and low survival rates. We designed a series of novel AuIII cyclometalated prodrugs of energy-disrupting Type II antidiabetic drugs namely, metformin and phenformin. Prodrug activation and release of the metformin ligand was achieved by tuning the cyclometalated AuIII fragment. The lead complex 3met was 6000-fold more cytotoxic compared to uncoordinated metformin and significantly reduced tumor burden in mice with aggressive breast cancers with lymphocytic infiltration into tumor tissues. These effects was ascribed to 3met interfering with energy production in TNBCs and inhibiting associated pro-survival responses to induce deadly metabolic catastrophe.

Aquaporins in cancer development: opportunities for bioinorganic chemistry to contribute novel chemical probes and therapeutic agents.

Aquaporins (AQPs) are membrane proteins allowing permeation of water, glycerol & hydrogen peroxide across biomembranes, and playing an important role in water homeostasis in different organs, exocrine gland secretion, urine concentration, skin moisturization, fat metabolism and neural signal transduction. Notably, a large number of studies showed that AQPs are closely associated with cancer biological functions and expressed in more than 20 human cancer cell types. Furthermore, AQP expression is positively correlated with tumour types, grades, proliferation, migration, angiogenesis, as well as tumour-associated oedema, rendering these membrane channels attractive as both diagnostic and therapeutic targets in cancer. Recent developments in the field of AQPs modulation have identified coordination metal-based complexes as potent and selective inhibitors of aquaglyceroporins, opening new avenues in the application of inorganic compounds in medicine and chemical biology. The present review is aimed at providing an overview on AQP structure and function, mainly in relation to cancer. In this context, the exploration of coordination metal compounds as possible inhibitors of aquaporins may open the way to novel chemical approaches to study AQP roles in tumour growth and potentially to new drug families. Thus, we describe recent results in the field and reflect upon the potential of inorganic chemistry in providing compounds to modulate the activity of "elusive" membrane targets as the aquaporins.