Induced-volatolomics for the design of tumour activated therapy.

The discovery of tumour-associated markers is of major interest for the development of selective cancer chemotherapy. Within this framework, we introduced the concept of induced-volatolomics enabling to monitor simultaneously the dysregulation of several tumour-associated enzymes in living mice or biopsies. This approach relies on the use of a cocktail of volatile organic compound (VOC)-based probes that are activated enzymatically for releasing the corresponding VOCs. Exogenous VOCs can then be detected in the breath of mice or in the headspace above solid biopsies as specific tracers of enzyme activities. Our induced-volatolomics modality highlighted that the up-regulation of N-acetylglucosaminidase was a hallmark of several solid tumours. Having identified this glycosidase as a potential target for cancer therapy, we designed an enzyme-responsive albumin-binding prodrug of the potent monomethyl auristatin E programmed for the selective release of the drug in the tumour microenvironment. This tumour activated therapy produced a remarkable therapeutic efficacy on orthotopic triple-negative mammary xenografts in mice, leading to the disappearance of tumours in 66% of treated animals. Thus, this study shows the potential of induced-volatolomics for the exploration of biological processes as well as the discovery of novel therapeutic strategies.

Volatile Organic Compound Based Probe for Induced Volatolomics of Cancers.

The development of efficient protocols for cancer diagnosis remains highly challenging. An emerging approach relies on the detection in exhaled breath of volatile organic compounds (VOC) produced by tumours. In this context, described here is a novel strategy in which a VOC-based probe is converted selectively in malignant tissues, by a tumour-associated enzyme, for releasing the corresponding VOC. The latter is then detected in the exhaled breath as a tumour marker for cancer diagnosis. This approach allows the detection of several different tumours in mice, the monitoring of tumour growth and tumour response to chemotherapy. Thus, the concept of "induced volatolomics" provides a new way to explore biological processes using VOC-based probes that could be adapted to many biomedical applications.

Identification of Phenolic Compounds-Rich Grape Pomace Extracts Urine Metabolites and Correlation with Gut Microbiota Modulation.

The high diversity of phenolic compounds (PC) found in food matrices makes it challenging to analyze their bioavailability and their impact on health and functional metabolism. It is well recognized that PC do modulate the composition of the gut microbiota (GM), however, the literature still lacks significant data concerning the link between the metabolic fate of the ingested compounds and their bioactivity, mainly when considering the secondary metabolites produced. In this study, we assessed the metabolic fate of PC for a period covering 14 months of daily intake to identify the metabolites that could be responsible for the effects of PC on the GM observed in our previous work. Urinary analysis of polyphenol metabolites was performed using a high resolution mass spectrometry LC-QTOF-MS method. Among the sixteen metabolites identified, 3-hydroxyphenylacetic acid and 2-(4-hydroxyphenyl) propionic acid were detected simultaneously and, therefore, correlated with the growth of Bifidobacterium in the rat GM. In addition, Daidzedin, detected only at 14 months post-treatment, mostly interfered with the growth inhibition of Clostridium (Cluster I). In conclusion, the impact of the long-term intake of PC on rat GM seems to be related to specific metabolites produced after ingestion of the parental compounds and this may also be due to their additional synergistic effects.