Periodic Reporting for period 2 - BOW (Biogenic Organotropic Wetsuits)
Okres sprawozdawczy: 2021-11-01 do 2023-04-30
Extracellular vesicles (EVs) are nanoparticles “made by cells for cells” which mediate physiological and pathological processes, at both the inter-cellular and inter-organism level.
The main goal of the BOW project is to explore and consolidate the technology able to impart biological precision, circulation and targeting abilities of EVs to superparamagnetic nanodevices (Magnetic Bead Devices, MBDs) by “dressing” them with a single- or multi-layer “wetsuit” of EV membrane “fabric”.
Specific objectives include production of high-grade EVs with biomimetic and organotropic functions, synthesis and functionalization of MBDs, engineering of a microfluidic device for streamlined fabrication of EV membrane-coated MBDs (evMBDs) and evaluation of evMBD biological performances in vitro, ex vivo and in vivo.
The BOW concept is (friendly) explained in the promotional video released on the project website (https://www.bowproject.eu) and YouTube.
The main goal of the BOW project is to explore and consolidate the technology able to impart biological precision, circulation and targeting abilities of EVs to superparamagnetic nanodevices (Magnetic Bead Devices, MBDs) by “dressing” them with a single- or multi-layer “wetsuit” of EV membrane “fabric”.
Specific objectives include production of high-grade EVs with biomimetic and organotropic functions, synthesis and functionalization of MBDs, engineering of a microfluidic device for streamlined fabrication of EV membrane-coated MBDs (evMBDs) and evaluation of evMBD biological performances in vitro, ex vivo and in vivo.
The BOW concept is (friendly) explained in the promotional video released on the project website (https://www.bowproject.eu) and YouTube.
# Action 1 “Production and characterization of the biogenic and synthetic building nanomaterials”.
- Small Extracellular Vesicles (sEVs) (biogenic nanomaterials, building blocks). Stable and reproducible batches of sEVs (< 250 nm) with narrow physicochemical properties from (i) human endometrial decidual tissue-derived mesenchymal stromal/stem cells (EDT-MSCs) and (ii) the microalgae marine chlorophyte Tetraselmis chuii (nanoalgosomes) are produced at full capacity for next needed use. The batches are validated and handled (including storage and shipping) by tailored standard procedures specifically implemented by the Consortium.
- Single- and multi-core iron oxide magnetic MBDs (synthetic nanomaterials, building blocks). The final prototypes of single- and multi-core magnetic bead devices (SC-MBDs and MC-MBDs) have been released and are now produced at full capacity for next needed use. SC-MBDs are 50 nm nanoparticles made of a superparamagnetic magnetite nanocore (10 nm) encased into a silica (SiO2) shell embedded with fluorescent molecules; MC-MBDs are slightly bigger, 70 nm, featuring 3 to 6 magnetite nanocores.
# Action 2 “Fabrication of the microfluidic dressing device”.
- Several prototypes of microfluidic device for transferring EV membranes onto MBDs – that is to realize hybrid nanoparticles made of EV-membrane coated MBDs (evMBDs) by processing EV and MBD building blocks – have been designed and fabricated. Some prototypes were successfully used for significant transferring of phospholipid membranes from EVs and liposomes (used as control) onto MBDs.
- Regarding evMBD characterization, methods have developed which pivot on cryo Electron Microscopy (cryo-EM), Atomic Force Microscopy (AFM), colloidal nanoplasmonics and compositional analytical techniques. At the same time, a first set of mathematical models have been developed.
# Action 3 “Testing of the nanotoxicology and of the biological performances”.
Also, thanks to the fact that the kick-off of this action was anticipated to the first year of activity, to counterbalance delays due to pandemic restrictions, investigation of in-vitro and in-vivo of the nanotoxicology and biological performances of the building blocks and the evMBDs is now at full speed yet providing key informative/baseline results.
# (Action 4) Management, exploitation, dissemination, communication, and training:
● 6 Consortium meetings;
● 7 Bimonthly technical meetings;
● 2 Technical meetings managed and participated by young researchers hired on the grant;
● 6 Ph.D. students hired on the grant;
● 9 Post-doc students hired on the grant;
● 3 Ph.D. student exchange between partners laboratories;
● 22 Scientific papers published open-access in peer-reviewed international scientific journals;
● 1 Book chapter;
● 6 Oral presentations at congresses;
● 3 Posters at congresses;
● 8 Open-access deliverables uploaded in public repositories indexed in OpenAIRE (Zenodo);
● 1 International Ph.D. winter school (extra deliverable) organized (http://venice2023.ibf.cnr.it);
● 1 Italian patent application filed (extra deliverable);
● 8 Key Exploitation Results (KERs);
● roadmap towards “BOW2”, targeting an EIC transition grant, laid down.
● 1 Promotional video released on the project website (https://www.bowproject.eu) and YouTube;
● 14 News in media;
● +200 Social tweets posted (https://twitter.com/BOWProjectEU)
- Small Extracellular Vesicles (sEVs) (biogenic nanomaterials, building blocks). Stable and reproducible batches of sEVs (< 250 nm) with narrow physicochemical properties from (i) human endometrial decidual tissue-derived mesenchymal stromal/stem cells (EDT-MSCs) and (ii) the microalgae marine chlorophyte Tetraselmis chuii (nanoalgosomes) are produced at full capacity for next needed use. The batches are validated and handled (including storage and shipping) by tailored standard procedures specifically implemented by the Consortium.
- Single- and multi-core iron oxide magnetic MBDs (synthetic nanomaterials, building blocks). The final prototypes of single- and multi-core magnetic bead devices (SC-MBDs and MC-MBDs) have been released and are now produced at full capacity for next needed use. SC-MBDs are 50 nm nanoparticles made of a superparamagnetic magnetite nanocore (10 nm) encased into a silica (SiO2) shell embedded with fluorescent molecules; MC-MBDs are slightly bigger, 70 nm, featuring 3 to 6 magnetite nanocores.
# Action 2 “Fabrication of the microfluidic dressing device”.
- Several prototypes of microfluidic device for transferring EV membranes onto MBDs – that is to realize hybrid nanoparticles made of EV-membrane coated MBDs (evMBDs) by processing EV and MBD building blocks – have been designed and fabricated. Some prototypes were successfully used for significant transferring of phospholipid membranes from EVs and liposomes (used as control) onto MBDs.
- Regarding evMBD characterization, methods have developed which pivot on cryo Electron Microscopy (cryo-EM), Atomic Force Microscopy (AFM), colloidal nanoplasmonics and compositional analytical techniques. At the same time, a first set of mathematical models have been developed.
# Action 3 “Testing of the nanotoxicology and of the biological performances”.
Also, thanks to the fact that the kick-off of this action was anticipated to the first year of activity, to counterbalance delays due to pandemic restrictions, investigation of in-vitro and in-vivo of the nanotoxicology and biological performances of the building blocks and the evMBDs is now at full speed yet providing key informative/baseline results.
# (Action 4) Management, exploitation, dissemination, communication, and training:
● 6 Consortium meetings;
● 7 Bimonthly technical meetings;
● 2 Technical meetings managed and participated by young researchers hired on the grant;
● 6 Ph.D. students hired on the grant;
● 9 Post-doc students hired on the grant;
● 3 Ph.D. student exchange between partners laboratories;
● 22 Scientific papers published open-access in peer-reviewed international scientific journals;
● 1 Book chapter;
● 6 Oral presentations at congresses;
● 3 Posters at congresses;
● 8 Open-access deliverables uploaded in public repositories indexed in OpenAIRE (Zenodo);
● 1 International Ph.D. winter school (extra deliverable) organized (http://venice2023.ibf.cnr.it);
● 1 Italian patent application filed (extra deliverable);
● 8 Key Exploitation Results (KERs);
● roadmap towards “BOW2”, targeting an EIC transition grant, laid down.
● 1 Promotional video released on the project website (https://www.bowproject.eu) and YouTube;
● 14 News in media;
● +200 Social tweets posted (https://twitter.com/BOWProjectEU)
BOW will proof and set a general, viable paradigm to recapitulate key biomimetic functions – including camouflage to the immune system and organ site/tumor targeting – of EVs to any synthetic nanodevice, while being disruptive as a first example of biogenic nanotechnology.
If successful, such a non-incremental technology will promote the progress of implantable nanodevices and nanomaterials towards sustainable production and clinical translation, contributing to strengthen and keep in the lead position European biotechnology and impacting life quality for people.
If successful, such a non-incremental technology will promote the progress of implantable nanodevices and nanomaterials towards sustainable production and clinical translation, contributing to strengthen and keep in the lead position European biotechnology and impacting life quality for people.