Biology subjects

Braeckmans, K.

Publications and source records attributed to Braeckmans, K..

5 recordsLinked to original sources

bioRxiv2026

Converting Lysosomes into Photothermal Organelles Enables Nanoparticle-Free Tumor Ablation via Intracellular Vapor Bubbles

Photothermal nanomaterials enable precise tumor ablation but face limitations in biodistribution, tissue penetration, toxicity, and biodegradability. Here, we present a unique concept for nanoparticle-free photothermal therapy based on the lysosomal entrapment of cationic amphiphilic small molecular dyes for spatially controlled vapor bubble (VB)-mediated tumor cell ablation. This strategy, which exploits a universal biological and physical effect, employs intracellular pH gradients for extensive local dye enrichment in acidified organelles, transforming them into transient endogenous nanosized photothermal reactors for subsequent light activation. Using sunitinib, a clinically approved lysosomotropic anticancer drug, and the commercially available dye LysoTracker Deep Red, lacking intrinsic anticancer activity, we demonstrate pulsed laser-induced VB formation specifically from dye-loaded lysosomes, leading to selective photomechanical disruption of various cancer cell models across 2D cultures, 3D spheroids, patient-derived neuroblastoma tumoroids and tumor fragments from an ovarian carcinoma patient. This approach allows precise, low-fluence and wavelength-tunable cancer tissue ablation without the need for synthetic photoresponsive nanoparticles.

bioengineering↗

bioRxiv2025

Lipid-stabilized ICG nanoaggregates for the photodisruption of vitreous opacities

Collagen aggregation in the vitreous is a major cause of vision impairment. Current treatments such as vitrectomy or YAG laser vitreolysis remain limited by invasiveness and safety concerns. In previous work, we introduced a novel approach combining indocyanine green (ICG) with nanosecond laser pulses to achieve photodisruption of collagen aggregates via vapor nanobubbles (VNBs), while using a significantly lower total light dose than that applied in clinical laser vitreolysis. However, despite its clinical approval, free ICG poses a risk of retinal toxicity. In this work, we report the development of ICG nanoaggregates (ICG AGG NPs) stabilized with a minimal amount of a hyaluronic acid (HA)-lipid (DOPE) conjugate designed to limit retinal penetration of ICG while preserving efficient VNB generation and collagen aggregate disruption. We demonstrate that supramolecular aggregation is a key requirement for efficient VNB generation, whereas encapsulation of ICG in conventional liposomes impairs this process. Using a newly established in vitro model for quantifying collagen disruption, we show that ICG AGG NPs significantly enhance photodisruption compared to free ICG. Furthermore, cell toxicity assays on retinal pigment epithelium (RPE) and Muller cells indicate that ICG AGG NPs maintain an acceptable safety profile at therapeutic concentrations. These findings represent the first successful demonstration of dye-loaded nanoparticles enabling efficient VNB-mediated photodisruption of vitreous opacities and highlight the promise of ICG AGG NPs as a safer and more effective alternative to free ICG for floater treatment.

biophysics↗

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↗

bioRxiv2025

DNA damage-associated vesicle production in Stenotrophomonas maltophilia is mediated by a cryptic tailocin endolysin

Like other Gram-negative bacteria, S. maltophilia is capable of producing membrane vesicles under normal growth conditions. The addition of certain exogenous triggers stimulates the production of vesicles, including those that are distinct from the archetypal outer membrane vesicle. In this study, we examine the effects of DNA damage on vesiculation, with a focus on the role of a bacteriophage-encoded endolysin. We demonstrate that deletion of the gene that encodes this protein (mal) negatively affects the vesiculation capacity of S. maltophilia. Further, we provide evidence that the spontaneous re-arrangement of shattered membrane fragments attributable to mal-induced explosive cell lysis results in the formation of predominantly explosive outer membrane vesicles, while only a minor portion are outer-inner membrane vesicles. Our findings expand on the current knowledge of (cryptic) tailocins in the biogenesis of vesicles in conditions of stress.

microbiology↗