Fanny Gassiot

Preclinical and clinical studies show that mild to moderate hypothermia is neuroprotective in sudden cardiac arrest, ischemic stroke, perinatal hypoxia/ischemia, traumatic brain injury and seizures. Induction of hypothermia largely involves physical cooling therapies, which induce several clinical complications, while some molecules have shown to b...

Preclinical and clinical studies show that mild to moderate hypothermia is neuroprotective in sudden cardiac arrest, ischemic stroke, perinatal hypoxia/ischemia, traumatic brain injury and seizures. Induction of hypothermia largely involves physical cooling therapies, which induce several clinical complications, while some molecules have shown to b...

Preclinical and clinical studies show that mild to moderate hypothermia is neuroprotective in sudden cardiac arrest, ischemic stroke, perinatal hypoxia/ischemia, traumatic brain injury and seizures. Induction of hypothermia largely involves physical cooling therapies, which induce several clinical complications, while some molecules have shown to b...

Preclinical and clinical studies show that mild to moderate hypothermia is neuroprotective in sudden cardiac arrest, ischemic stroke, perinatal hypoxia/ischemia, traumatic brain injury and seizures. Induction of hypothermia largely involves physical cooling therapies, which induce several clinical complications, while some molecules have shown to b...

Preclinical and clinical studies show that mild to moderate hypothermia is neuroprotective in sudden cardiac arrest, ischemic stroke, perinatal hypoxia/ischemia, traumatic brain injury and seizures. Induction of hypothermia largely involves physical cooling therapies, which induce several clinical complications, while some molecules have shown to b...

Here we report the coupling of a cyclic peptide (VH4127) targeting the low density lipoprotein (LDL) receptor (LDLR) noncompetitively to cucurbit[7]uril (CB[7]) to develop a new kind of drug delivery system (DDS), namely, CB[7]-VH4127, with maintained binding affinity to the LDLR. To evaluate the uptake potential of this bismacrocyclic compound, an...

Despite clinical advances in diagnosis and treatment, pancreatic ductal adenocarcinoma (PDAC) remains the third leading cause of cancer death, and is still associated with poor prognosis and dismal survival rates. Identifying novel PDAC-targeted tools to tackle these unmet clinical needs is thus an urgent requirement. Here we use a peptide conjugat...

Targeted delivery to specific tissues and subcellular compartments is of paramount importance to optimize therapeutic or diagnostic interventions while minimizing side-effects. Using recently identified LDL receptor (LDLR) -targeting small synthetic peptide-vectors conjugated to model cargos of different nature and size, we investigated in LDLR-exp...

Insufficient membrane penetration of drugs, in particular biotherapeutics and/or low target specificity remain a major drawback in their efficacy. We propose here the rational characterization and optimization of peptides to be developed as vectors that target cells expressing specific receptors involved in endocytosis or transcytosis. Among recept...

Intracellular delivery of vector-cargo conjugates in endo-lysosomal vesicular compartments in CHO-hLDLR-EGFP cells. (A) Pulse-chase analysis of the lysosomal delivery of DiI-LDL (red). DiI-LDL 20 μg/mL was incubated on CHO-hLDLR-EGFP cells for 30 min at 4°C (pulse). At the end of a 3 hr incubation period in ligand-free medium (chase), LysoTracker®...

SPR measurement of free and conjugated peptides binding on immobilized LDLR. LDLR was captured on NiHC1000m sensor chips and increasing concentrations of analytes (50–800 nM for VH411, VH411-S-Tag, VH04sc, VH445, VH445-S-Tag and VH434; 10–160 nM for VH4127, VH4127-S-Tag, Cy5.5-PEG6-VH4127 and SiGLO CyclophilineB-VH4127; 1–16 nM for VH445 Dimer; 0.1...

Scheme describing the overall approach for identification, optimization and in vitro/vivo validation of LDLR targeting peptide vectors and conjugates. Step1: Hit peptides that recognize and bind to the hLDLR expressed in stable CHO cell lines are identified by screening of bacteriophage libraries presenting cyclic and linear peptides. Step2: Peptid...

Identity, sequences and mass of LDLR targeting peptides, free or conjugated/fused to different molecules. (PDF)

Active targeting and delivery to pathophysiological organs of interest is of paramount importance to increase specific accumulation of therapeutic drugs or imaging agents while avoiding systemic side-effects. We recently developed a family of new peptide ligands of the human and rodent LDL-receptor (LDLR), an attractive cell-surface receptor with h...

Efforts were made to improve a series of potent dual ABL/SRC inhibitors based on a 7-azaindole core with the aim of developing compounds that demonstrate a wider activity on selected oncogenic kinases. Multi-Targeted Kinase Inhibitors (MTKIs) were then derived, focusing on kinases involved in both angiogenesis and tumorigenesis processes. Anti-prol...