Biology subjects

Le Guevel, X.

Publications and source records attributed to Le Guevel, X..

6 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↗

bioRxiv2025

Self-Assembled siRNA-Gold Supraclusters Detected at the Single-Molecule Level in the NIR-II Window

Gold nanoclusters (AuNCs) possess unique photophysical properties that make them excellent candidates for advanced bioimaging and single-particle detection. In this work, we report the self-assembly of highly emissive, positively charged NIR-II AuNCs stabilized by cysteamine, directed by small interfering RNA (siRNA), which serves as both a structural and electrostatic modulator. The resulting supramolecular assemblies exhibit quasi-spherical morphologies around 100 nm in diameter, with outstanding colloidal stability, photostability, and enzymatic resistance. Their strong photoluminescence, extending up to 1400 nm, enables robust single- particle detection in solution. Spectroscopic and structural analyses--including fluorescence spectroscopy, small-angle X-ray scattering (SAXS), and single-particle tracking--highlight the pivotal role of siRNA in tuning the assembly process via charge balance and concentration- dependent interactions. Beyond providing insights into the structural and photophysical behavior of nucleic acid-guided AuNC assemblies, these results underscore their promise as multifunctional nanoplatforms for integrated imaging and gene-silencing therapies in biophotonic and theranostic applications.

bioengineering↗

bioRxiv2025

Interplay Between Intrinsically Disordered Proteins and Atomically Precise Gold Nanoclusters Modulates their Optical Properties

Understanding how structural and optical properties of metallic nanoclusters can be tuned by proteins is crucial for the use of these hybrid molecules in biomedical applications. The interaction of proteins with ultrasmall, atomically-precise gold nanoclusters (Au-NCs) has been mainly investigated in the context of structured proteins, while their behavior with intrinsically disordered proteins (IDPs) remains unexplored. This work examines the structural and optical properties of Au-NCs interacting with bioengineered IDPs containing up to three cysteines. We show that, by exploiting the conformational flexibility of cysteine-containing IDPs, we can anchor proteins to Au-NCs in a position-specific manner, leading to new bioconjugates with properties that differ from those of the individual components. We observed an up to 15-fold photoluminescence enhancement depending on the number of cysteines anchored. By combining mass spectrometry, small-angle X-ray scattering (SAXS), and computational modelling, the ensemble structures of nine bioconjugates with different stoichiometries were elucidated, indicating their overall compactness. Our results suggest that the interface between these atomically-precise species and the conformationally fluctuating protein is responsible for the optical properties of these nanobioconjugates. This research improves our understanding of Au-NC- protein interactions, paving the way to novel nano-molecular hybrid conjugates with tunable properties for bioimaging and therapeutic applications.

biochemistry↗

bioRxiv2021

Protein corona modulates interaction of spiky nanoparticles with lipid bilayers

The impact of protein corona on the interactions of nanoparticles (NPs) with cells remains an open question. This question is particularly relevant to NPs which sizes, ranging from tens to hundreds nanometers, are comparable to the sizes of most abundant proteins in plasma. Protein sizes match with typical thickness of various coatings and ligands layers, usually present at the surfaces of larger NPs. Such size match may affect the properties and the designed function of NPs. We offer a direct demonstration of how protein corona can dramatically change the interaction mode between NPs and lipid bilayers. To this end, we choose the most extreme case of NP surface modification: nanostructures in the form of rigid spikes of 10-20 nm length at the surface of gold nanoparticles. In the absence of proteins we observe the formation of reversible pores when spiky NPs absorb on lipid bilayers. In contrast, the presence of bovine serum albumin (BSA) proteins adsorbed at the surface of spiked NPs, effectively reduce the length of spikes exposed to the interaction with lipid bilayers. Thus, protein corona changes qualitatively the dynamics of pore formation, which is completely suppressed at high protein concentrations. These results suggest that protein corona can not only be critical for interaction of NPs with membranes, it may change their mode of interaction, thus offsetting the role of surface chemistry and ligands.

biophysics↗

bioRxiv2021

Deep learning image analysis for in vivo shortwave infrared imaging

Shortwave infrared window (SWIR: 1000-1700 nm) represents a major improvement compared to the NIR-I region (700-900 nm) in terms of temporal and spatial resolutions in depths down to 4 mm. SWIR is a fast and cheap alternative to more precise methods such as X-ray and opto-acoustic imaging. Main obstacles in SWIR imaging are the noise and scattering from tissues and skin that reduce the precision of the method. We demonstrate that the combination of SWIR in vivo imaging in the NIRIIb region (1500-1700 nm) with advanced deep learning image analysis allows to overcome these obstacles and making a large step forward to high resolution imaging: it allows to precisely segment vessels from tissues and noise, provides morphological structure of the vessels network, with learned pseudo-3D shape, their relative position, dynamic information of blood vascularization in depth in small animals and distinguish the vessels types: artieries and veins. For demonstration we use neural network IterNet that exploits structural redundancy of the blood vessels, which provides a useful analysis tool for raw SWIR images.

cancer biology↗

bioRxiv2020

Non-invasive, Real-time Detection of Vascular Disorders in Mice using Bright SWIR-emitting Gold Nanoclusters and Monte Carlo Image Analysis

We present here a new approach for non-invasive high resolution whole-body vascular imaging in depth by combining water-soluble and bright SWIR-emitting gold nanoclusters revealing an anisotropic surface charge with Monte Carlo image processing of the images. We applied and validated this approach to quantify vessel complexity in transgenic mice presenting vascular disorders.

bioengineering↗