Shopping Cart (0)
My Account

Shopping Cart
SELECTBIO Conferences Extracellular Vesicles & Nanoparticle Therapeutics Europe 2022


From Small Molecules to Proteins and Nanoparticles: Exploring Novel Tools For Intracellular Delivery

Koen Raemdonck, Professor, Ghent University

Intracellular delivery of membrane-impermeable cargo (e.g. nucleic acid- or protein-based drugs) provides unique opportunities for cell biology and biomedical applications. A wide variety of intracellular delivery technologies is available to date, such as carrier- and membrane disruption-based approaches. However, existing tools are often suboptimal and alternative technologies that merge delivery efficiency, biocompatibility and applicability remain highly sought after. This presentation will first describe the repurposing of two distinct cationic amphiphiles, i.e. both low molecular weight cationic amphiphilic drugs (CADs) as well as lung surfactant-inspired proteins and peptides, to improve cellular delivery of RNA therapeutics. Both approaches significantly promote cytosolic RNA delivery, albeit by adopting a different mode-of-action for permeabilization of the endosomal and/or lysosomal compartments. In contrast to carrier-based protocols, physical delivery approaches do not rely on the endosomal pathway and allow the direct cytosolic access of cell-impermeable agents. Our group recently developed two innovative physical delivery technologies based on non-viral nanoparticles that can be implemented in cell engineering protocols. One platform (Hydrogel-enabled nanoPoration or HyPore) exploits cationic hydrogel nanoparticles to disrupt the plasma membrane of cells, enabling cytosolic delivery of nanobodies and enzymes. Of note, HyPore-mediated delivery of the neutral MRI contrast agent gadobutrol significantly improved T1-weighted MRI signal intensities in primary human T cells, outperforming state-of-the-art nucleofection. A second platform technology is nanoparticle-sensitized photoporation. By attaching photothermal nanoparticles to the cell surface followed by pulsed laser illumination, transient membrane pores can be generated that allow delivery of biologics into cells with high efficiency. To avoid direct contact of the nanoparticles with cells and the associated regulatory concerns, light-sensitive iron oxide nanoparticles were embedded in electrospun nanofibers. The resulting photothermal electrospun nanofibers (PENs) successfully delivered CRISPR-Cas9 ribonucleoprotein complexes and siRNAs into embryonic stem cells and T cells, while maintaining cellular fitness and phenotype (6). In conclusion, the above described approaches are considered promising concepts towards improved cellular delivery of a wide variety of cargo for biomedical applications.

Add to Calendar ▼2022-10-24 00:00:002022-10-25 00:00:00Europe/LondonExtracellular Vesicles and Nanoparticle Therapeutics Europe 2022Extracellular Vesicles and Nanoparticle Therapeutics Europe 2022 in Rotterdam, The NetherlandsRotterdam, The