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Dresden 2026 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 14: Poster Session II

BP 14.31: Poster

Dienstag, 10. März 2026, 18:00–21:00, P2

Receptor-Mediated Binding Kinetics of Ligand-Functionalized Lipid Nanoparticles for Targeted mRNA Delivery — •Tianyi Cao — Faculty of Physics and Center for NanoScience, Ludwig Maximilians University, Munich 80539, Germany

For targeted mRNA delivery, lipid nanoparticles (LNPs) are functionalized with PEG-lipid tethers that display affinity ligands--such as full antibodies, Fab fragments, or peptides--to enable receptor-specific cell binding.

We establish a quantitative single-cell binding assay to characterize these receptor-mediated interactions using functionalized LNPs. Using time-lapse live-cell imaging on single-cell arrays (LISCA), we track individual particles via fluorophore-labeled lipid components incorporated directly into the LNP membrane. We systematically vary the molar fraction of functionalized PEG-lipids to quantify how ligand density influences binding probability and saturation behavior.

From these trajectories we extract apparent on-rates, binding capacities, and cell-to-cell variability arising from heterogeneous receptor expression. Under controlled shear flow, we distinguish diffusion-limited from reaction-limited binding and quantify how hydrodynamic forces modulate bond formation and stability.

We further extend the framework to multivalent LNPs carrying mixtures of different ligands that target distinct receptors on the same cell. This assay provides a mechanistic, single-cell-resolved readout of receptor-mediated LNP binding, enabling rational optimization of selective mRNA delivery formulations.

Keywords: Nanoparticle binding kinetics; Receptor-mediated interactions; Single-cell imaging

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