Biology subjects

De Smedt, S.

Publications and source records attributed to De Smedt, S..

3 recordsLinked to original sources

bioRxiv2025

Photothermal transport for guiding nanoparticles through the vitreous humor

Visual impairments affect over 2.2 billion people worldwide, yet delivering drugs to the eyes posterior segment, including the retina, remains a major challenge. Intravitreal injection, the standard administration route to the posterior segment of the eye, often results in suboptimal drug diffusion through the vitreous, preventing drugs from reaching the retina. While various strategies have been explored to enhance the mobility of drug molecules and nanomedicines (drugs encapsulated in nanoparticles) in the vitreous, no method has demonstrated guided transport of drugs and particles through the vitreous. In this study, we explore photothermal transport of nanoparticles in the vitreous using a pulsed-laser and indocyanine green added to the vitreous, both being clinically approved modalities. We found that photothermal transport allows to guide nanoparticles from one place in the vitreous towards the laser illuminated area in the vitreous, at a distance of the injection spot of the nanoparticles. Using multiple-particle tracking and numerical simulations, we found that both thermal convection and thermophoresis contribute to photothermal transport of nanoparticles in the vitreous. We identified parameters for optimizing this effect, including dye concentration, particle size, distance from the laser focus, and laser fluence. Our findings establish a novel and clinically relevant paradigm for light-guided drug delivery in the eye. This study represents, to our knowledge, the first demonstration of guided light-controlled particle transport in the vitreous using ocular dyes and pulsed-lasers which are routinely used in ophthalmology.

biophysics↗

bioRxiv2025

Photodisruption of the inner limiting membrane promotes retinal engraftment of stem-cell derived retinal ganglion cells

Glaucoma is the leading cause of irreversible blindness, driven by the progressive loss of retinal ganglion cells (RGCs). Stem cell-derived RGC transplantation could revolutionize glaucoma treatment, but the inner limiting membrane (ILM) remains a major obstacle by hindering cell migration into the retina. Interestingly, the ILM represents a double-edged sword for RGC engraftment: on the one hand, it greatly hinders cell migration, whereas on the other hand, its presence during retinal development is necessary for neuronal migration and retinal lamination. As an alternative to current invasive and harmful strategies to disrupt the ILM, we introduce ILM photodisruption, a minimally invasive biophotonic method that can manipulate the integrity of the ILM with unprecedented precision. In this study, we have finetuned the technology in bovine and human organotypic retinal explants to create templated ILM pores, creating entryways for donor RGCs to enter the retina while preserving most of the membrane to confer guidance cues for their engraftment. Applying this technology, we were able to promote donor RGC survival, enhance cell spreading and facilitate integration into the retina. Overall, our findings demonstrate that ILM photodisruption effectively addresses a key barrier in RGC replacement, paving the way for advancing retinal regeneration toward clinical application.

pharmacology and toxicology↗

bioRxiv2022

Immunopeptidomics-based design of highly effective mRNA vaccine formulations against Listeria monocytogenes

Listeria monocytogenes is a foodborne intracellular bacterial pathogen leading to human listeriosis. Despite a high mortality rate and increasing antibiotic resistance no clinically approved vaccine against Listeria is available. Attenuated Listeria strains offer protection and are tested as antitumor vaccine vectors, but would benefit from a better knowledge on immunodominant vector antigens. To identify novel antigens, we screened for Listeria epitopes presented on the surface of infected human cell lines by mass spectrometry-based immunopeptidomics. In between more than 15,000 human self-peptides, we detected 68 Listeria epitopes from 42 different bacterial proteins, including several known antigens. Peptide epitopes presented on different cell lines were often derived from the same bacterial surface proteins, classifying these antigens as potential vaccine candidates. Encoding these highly presented antigens in lipid nanoparticle mRNA vaccine formulations resulted in specific CD8+ T-cell responses and high levels of protection in vaccination challenge experiments in mice. Our results pave the way for the development of a clinical mRNA vaccine against Listeria and aid to improve attenuated Listeria vaccines and vectors, demonstrating the power of immunopeptidomics for next-generation bacterial vaccine development.

immunology↗