Title : Designing extracellular vesicles for bio-camouflaged drug delivery and cell-free regenerative medicine
Extracellular vesicles (EVs) are multifaceted subcellular entities that may represent a new generation of bio-camouflaged drug/ nanoparticle delivery system and regenerative medicine effectors. In a top-down procedure, our group has engineered nanoparticle/drug-loaded EVs from precursor cells previously loaded with this cargo. EVs from HUVEC cells and THP1 macrophages were tested for anti-tumor therapy. Concerning regenerative medicine, EVs were obtained from adipose stem cells and tested in a fistula model. By using our method, EVs could encapsulate a set of nanoparticles regardless their chemistry or shape. These hybrid vesicles were able to generate heat when submitted to an alternating magnetic field and could be monitored by fluorescence imaging or MRI. Dual drug/nanoparticle EV loading was also feasible by this method. We demonstrated that vesicles from THP-1 cells could be loaded with iron oxide nanoparticles and different therapeutic agents irrespective to their molecular weight, hydrophobic, hydrophilic and amphiphilic character. The theranostic potential of mTHPC-loaded magnetic EVs was tested in vivo in a murine tumoral model. Vesicles could be tracked in vivo by dual-mode imaging, combining optical imaging and MRI. The engineered EVs were found to induce an efficient photodynamic action, as evidenced by tumor growth curves and histological analysis. The regenerative properties of EVs obtained from adipose stem cells was demonstrated in a fistula model. In brief, we succeeded in customizing EV by engineering them to display several nanoparticle/drug cargoes featuring therapeutic and imaging properties both in vitro and in vivo. EV regenerative effect was for the first time demonstrated for fistula therapy.
Audience take away:
• How we can convert biological messengers into a bio-camouflaged delivery system
• Production and engineering methods to do so.
• In vitro and in vivo properties of the designed extracellular vesicles.