Biology subjects

Dupont, E.

Publications and source records attributed to Dupont, E..

3 recordsLinked to original sources

bioRxiv2025

Radiotherapy Enhancement by Gold Nanocluster-functionalized Nanoliposomes Using Polychromatic Orthovoltage X-ray Irradiation

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, as the most effective chemoradiation therapies achieve unsatisfactory outcomes while associated with high toxicity. Nanoliposomal drug delivery systems are widely used to improve chemotherapy safety, yet passive release of amphiphilic drugs may still associate with adverse toxicity. To address this, we previously developed nanoliposomes functionalized with hydrophobic gold nanoclusters, demonstrating radiocatalytic activity and enhanced chemoradiotherapy effects in 3D PDAC microtumors under synchrotron irradiation. In this study, gold nanocluster-functionalized nanoliposomes (AuLPs) were optimized and evaluated under 220 kVp orthovoltage X-ray irradiation, widely used in preclinical irradiation systems. AuLPs containing 0.2 mol% gold nanoclusters produced 1.5-fold more reactive oxygen species than unloaded liposomes. However, higher molar ratios were necessary to improve radiotherapy outcomes in 3D PDAC microtumor models following 4 and 8 Gy irradiation. Pharmacokinetics and biodistribution evaluations showed a modest increase in tumor gold content 24 hours post-injection in orthotopic PDAC models. Altogether, these results underscore the potential of gold-radiotherapy-responsive liposomes while highlighting critical formulation challenges, which must be resolved for full therapeutic potential.

bioengineering↗

bioRxiv2022

ENGRAILED-1 transcription factor exerts a paracrine neurotrophic activity on adult spinal cord α-motoneurons.

Several homeoprotein transcription factors transfer between cells and regulate gene expression, protein translation, and chromatin organization in recipient cells. ENGRAILED-1 is one such homeoprotein expressed in spinal V1 interneurons synapsing on -motoneurons. Neutralizing extracellular ENGRAILED-1 by expressing a secreted single-chain antibody blocks its capture by spinal motoneurons resulting in -motoneurons loss and limb weakness. A similar but stronger phenotype is observed in the Engrailed-1 heterozygote mouse, confirming that ENGRAILED-1 exerts a paracrine neurotrophic activity on spinal cord -motoneurons. Intrathecal injection of ENGRAILED-1 leads to its specific internalization by spinal motoneurons and has long-lasting protective effects against neurodegeneration and weakness. Midbrain dopaminergic neurons express Engrailed-1 and, similarly to spinal cord -motoneurons, degenerate in the heterozygote. By identifying genes expressed in spinal cord motoneurons also showing modified expression in mouse Engrailed-1 heterozygote midbrain neurons, we identified p62/SQTSM1 as an age marker in spinal cord motoneurons with increased expression during aging, in the Engrailed-1 heterozygote and upon extracellular ENGRAILED-1 neutralization. We conclude that ENGRAILED-1 is a regulator of motoneuron ageing with non-cell autonomous neurotrophic activity.

neuroscience↗

bioRxiv2020

Bidirectional transfer of Engrailed homeoprotein across the plasma membrane requires PIP2

1.Homeoproteins are a class of transcription factors sharing the unexpected property of intercellular trafficking. It confers to homeoproteins a paracrine mode of action, shown to exert a wide range of physiological functions, during development and in the adult. Internalization and secretion, the two steps of intercellular transfer, rely on unconventional mechanisms but the cellular mechanisms at stake still need to be fully characterized. Thanks to the design of new quantitative and sensitive assays dedicated to the study of homeoprotein transfer in cell culture, we demonstrate a core role of the phosphoinositides PIP2 together with cholesterol in the translocation of Engrailed2 (EN2) homeoprotein across the plasma membrane. Both secretion and internalization are regulated according to PIP2 levels, challenged by drug or enzymatic treatments. In addition, EN2 specifically interacts with PIP2 and the reduced affinity of a paracrine deficient mutant of EN2 supports a role of PIP2 in homeoprotein physiological function. We propose that the two ways plasma membrane translocation steps accounting for homeoprotein secretion and internalization respectively are parts of a common process. Summary StatementDeciphering the mechanism of homeoprotein intercellular trafficking

cell biology↗