Biology subjects

D'Ancona, C.

Publications and source records attributed to D'Ancona, C..

2 recordsLinked to original sources

bioRxiv2025

iSleep: Continuous, binocular pupil tracking in sleep and reduced consciousness for physiological monitoring, predictions and interventions

Monitoring pupil dynamics is a key tool in understanding arousal. Pupil size can serve as a biomarker for the autonomic nervous system balance as well as for identifying brain states. While internal states can also be self-reported when awake, automated detection and non-invasive monitoring is crucial during sleep and reduced consciousness. Here, we introduce iSleep, an innovative pupil tracking and analysis framework for sleep in humans. It features comfortable, humidified eye-tracking goggles and a platform for integrated analysis and prediction capabilities. We show that iSleep allows safe and continuous access to binocular pupil size and ocular dynamics during sleep and anesthesia. iSleep reveals that pupillary fluctuations correlate tightly with brain activity, heartbeat, and breathing, and can reliably predict brain states. Pupil constrictions reflect parasympathetic drive and likely serve a protective function for deep sleep stability; while dilations indicate arousals. Unexpectedly, we observed a decoupling of binocular movements during periods of sleep, indicating alterations in reflexes which usually govern voluntary eye movements. Finally, iSleep was tested in surgery patients under general anesthesia, revealing dynamic pupil changes to noxious stimuli, suggesting the potential for nociception monitoring during surgeries. In summary, iSleep offers an easy-to-use, robust alternative to read out brain states during sleep and anesthesia, opening new avenues in monitoring, diagnostics, and treatments, previously obscured by closed eyelids.

neuroscience↗

bioRxiv2024

New therapeutic combination to enhance endocytosis of antibodies and nucleic-acid aptamers targeting EGFR in glioblastoma cells

Active targeting is based on the binding of ligands to receptors present on the surface of targeted cells, in order to promote the internalization of the drugs conjugated to the ligands. Several conjugates are already in use or under development for active targeting of tumors, the most widely known being antibody-drug conjugates (ADC). They combine the specificity of monoclonal antibodies with the cytotoxicity of chemotherapeutic molecules. Other than antibodies, nucleic-acid aptamers, are promising ligands to deliver conjugated drugs by active targeting in tumor cells. The therapeutic efficacy of conjugates largely depends on their endocytosis and vesicular trafficking. However, so far, no therapeutic approach to enhance endocytosis of conjugates is available. In recent studies, we showed that gefitinib, a tyrosine kinase inhibitor directed against the epidermal growth factor receptor EGFR, induces a massive, non-physiological endocytosis of EGFR, known as gefitinib-mediated endocytosis (GME), in different glioblastoma cell lines. We thus hypothesized that besides promoting endocytosis of EGFR, gefitinib could also promote endocytosis of its ligands. In this study, we proved by quantitative fluorescence bioimaging, that gefitinib is indeed able to strengthen the endocytosis of fluorophore-conjugated EGFR-specific antibodies and aptamers. We also showed that the GME potentiates the toxicity of an antibody-drug conjugate, even at low concentrations. Our results suggest the development of a new therapeutic combination, of ADC and gefitinib, to potentiate the delivery of ADC and likely other conjugates targeting EGFR in glioblastoma, while limiting side effects on non-targeted cells.

cell biology↗