publications of the research group biogenic nanotherapeutics ([HIPS] BION)
group leader: Dr. Fuhrmann
Extracellular vesicles protect glucuronidase model enzymes during freeze-drying.(2018-08-17)Extracellular vesicles (EVs) are natural nanoparticles that play important roles in intercellular communication and are increasingly studied for biosignalling, pathogenesis and therapy. Nevertheless, little is known about optimal conditions for their transfer and storage, and the potential impact on preserving EV-loaded cargoes. We present the first comprehensive stability assessment of different widely available types of EVs during various storage conditions including -80 °C, 4 °C, room temperature, and freeze-drying (lyophilisation). Lyophilisation of EVs would allow easy handling at room temperature and thus significantly enhance their expanded investigation. A model enzyme, β-glucuronidase, was loaded into different types of EVs derived from mesenchymal stem cells, endothelial cells and cancer cells. Using asymmetric flow field-flow fractionation we proved that the model enzyme is indeed stably encapsulated into EVs. When assessing enzyme activity as indicator for EV stability, and in comparison to liposomes, we show that EVs are intrinsically stable during lyophilisation, an effect further enhanced by cryoprotectants. Our findings provide new insight for exploring lyophilisation as a novel storage modality and we create an important basis for standardised and advanced EV applications in biomedical research.
Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy.(2018-02-23)Extracellular vesicles (EVs) have recently gained significant attention as important mediators of intercellular communication, potential drug carriers, and disease biomarkers. These natural cell-derived nanoparticles are postulated to be biocompatible, stable under physiological conditions, and to show reduced immunogenicity as compared to other synthetic nanoparticles. Although initial clinical trials are ongoing, the use of EVs for therapeutic applications may be limited due to undesired off-target activity and potential "dilution effects" upon systemic administration which may affect their ability to reach their target tissues. To fully exploit their therapeutic potential, EVs are embedded into implantable biomaterials designed to achieve local delivery of therapeutics taking advantage of enzyme prodrug therapy (EPT). In this first application of EVs for an EPT approach, EVs are used as smart carriers for stabilizing enzymes in a hydrogel for local controlled conversion of benign prodrugs to active antiinflammatory compounds. It is shown that the natural EVs' antiinflammatory potential is comparable or superior to synthetic carriers, in particular upon repeated long-term incubations and in different macrophage models of inflammation. Moreover, density-dependent color scanning electron microscopy imaging of EVs in a hydrogel is presented herein, an impactful tool for further understanding EVs in biological settings.
Extracellular vesicles - A promising avenue for the detection and treatment of infectious diseases?(2017-04-07)Extracellular vesicles (EVs) have gained increasing attention as novel disease biomarkers and as promising therapeutic agents. These cell-derived, phospholipid-based particles are present in many - if not all - physiological fluids. They have been shown to govern several physiological processes, such as cell-cell communication, but also to be involved in pathological conditions, for example tumour progression. In infectious diseases, EVs have been shown to induce host immune responses and to mediate transfer of virulence or resistance factors. Here, we discuss recent developments in using EVs as diagnostic tools for infectious diseases, the development of EV-based vaccines and the use of EVs as potential anti-infective entity. We illustrate how EV-based strategies could open a viable new avenue to tackle current challenges in the field of infections, including barrier penetration and growing resistance to antimicrobials.