Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Tuesday Speaker Abstracts

Fusion of Synthetic Lipid Carriers to Exosomes Produces Hybrid Vesicles Harnessed for the Delivery of Biomolecules Joël De Beer , ETH Zürich, Zürich, Switzerland. The release of native extracellular vesicles (EVs) by virtually all cells in the body, has emerged as a crucial mechanism for communication between neighboring and distant cells. Researchers are trying to harness this natural way of communication to deliver therapeutics into cells of interest. Using these natural intercellular communicators as potent drug carriers requires the ability of loading therapeutic cargo into the vesicles. The current loading methods raise safety and/or scalability concerns as they involve bioengineering or vigorous membrane manipulation. Conversely, synthetic vesicles made by modern nanotechnological methods have a high therapeutic loading. Thus a method has been devised combining the loading capacity of synthetic vesicles with the complex surface structure of EVs in a hybrid carrier by fusion. The assembly of this hybrid carrier, termed “hybridosome”, was demonstrated in bulk (lipid mixing, light scattering) and at a single particle level (fluorescence cross-correlation spectroscopy, nanoparticle tracking). The underlying fusion mechanism is simultaneously inducible and self- limiting, offering a self-assembly method that is predictable and independent of bioengineering. All synthetic membrane constituents are non-toxic and FDA approved or currently in advanced clinical trials. An in vitro proof-of-concept based on hybridosomes from glioblastoma-derived EVs and GFP reporter gene encapsulating synthetic vesicle, showed fast and functional gene delivery into glioblastoma cells. Hybridosome versatility was demonstrated by encapsulating nucleic acids, proteins and gold nanoparticles. Moreover, hybridosomes were decorated with PEG, antibody fragments and peptides, emphasizing that hybridosomes can additionally be tailored for cellular targeting and crossing biological membranes. The findings were extended to EVs derived from primary human platelets and neutrophils. By presenting functional hybridosomes encapsulating both therapeutic and diagnostic agents, this new delivery platform allows legitimate prospects in several biomedical applications.

28