Biology subjects

Elleaume, H.

Publications and source records attributed to Elleaume, H..

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↗

bioRxiv2023

A novel injectable radiopaque hydrogel with potent properties for multicolor CT imaging in the context of brain and cartilage regenerative therapy

Cell therapy is promising to treat many conditions, including neurological and osteoarticular diseases. Encapsulation of cells within hydrogels facilitates cell delivery and can improve therapeutic effects. However, much work remains to be done to align treatment strategies with specific diseases. The development of imaging tools that enable monitoring cells and hydrogel independently is key to achieving this goal. Our objective herein is to longitudinally study an iodine-labeled hydrogel, incorporating gold-labeled stem cells, by bicolor CT imaging after in vivo injection in rodent brains or knees. To this aim, an injectable self-healing hyaluronic acid (HA) hydrogel with long-persistent radiopacity was formed by the covalent grafting of a clinical contrast agent on HA. The labeling conditions were tuned to achieve sufficient X-ray signal and to maintain the mechanical and self-healing properties as well as injectability of the original HA scaffold. The efficient delivery of both cells and hydrogel at the targeted sites was demonstrated by synchrotron K-edge subtraction-CT. The iodine labeling enabled to monitor the hydrogel biodistribution in vivo up to 3 days post-administration, which represents a technological first in the field of molecular CT imaging agents. This tool may foster the translation of combined cell-hydrogel therapies into the clinics.

bioengineering↗

bioRxiv2021

Brain virtual histology with X-ray phase-contrast tomography Part I: whole-brain myelin mapping in white-matter injury models

White-matter injury leads to severe functional loss in many neurological diseases. Myelin staining on histological samples is the most common technique to investigate white-matter fibers. However, tissue processing and sectioning may affect the reliability of 3D volumetric assessments. The purpose of this study was to propose an approach that enables myelin fibers to be mapped in the whole rodent brain with microscopic resolution and without the need for strenuous staining. With this aim, we coupled inline (propagation-based) X-ray phase-contrast tomography (XPCT) to ethanol-induced brain sample dehydration. We here provide the proof-of-concept that this approach enhances myelinated axons in rodent and human brain tissue. In addition, we demonstrated that white-matter injuries could be detected and quantified with this approach, using three animal models: ischemic stroke, premature birth and multiple sclerosis. Furthermore, in analogy to diffusion tensor imaging (DTI), we retrieved fiber directions and DTI-like diffusion metrics from our XPCT data to quantitatively characterize white-matter microstructure. Finally, we showed that this non-destructive approach was compatible with subsequent complementary brain sample analysis by conventional histology. In-line XPCT might thus become a novel gold-standard for investigating white-matter injury in the intact brain. This is Part I of a series of two articles reporting the value of in-line XPCT for virtual histology of the brain; Part II shows how in-line XPCT enables the whole-brain 3D morphometric analysis of amyloid-{beta} (A{beta}) plaques. HighlightsO_LIX-ray phase-contrast tomography (XPCT) enables myelin mapping of the whole brain C_LIO_LIXPCT detects and quantifies white-matter injuries in a range of diseases C_LIO_LIFiber directions and anisotropy metrics can be retrieved from XPCT data C_LIO_LIXPCT is compatible with subsequent conventional histology of brain samples C_LIO_LIXPCT is a powerful virtual histology tool that requires minimal sample preparation C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=130 SRC="FIGDIR/small/436852v3_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@1b06ba6org.highwire.dtl.DTLVardef@16b8d4aorg.highwire.dtl.DTLVardef@91cfborg.highwire.dtl.DTLVardef@4dcbca_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗