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New nanomaterials for neural stem cells drug delivery

Periodic Reporting for period 2 - NANOSTEM (New nanomaterials for neural stem cells drug delivery)

Reporting period: 2020-06-01 to 2022-05-31

Brain conditions such as neurodegenerative diseases, stroke, and traumatic injuries are a significant burden in modern society. Multiple therapeutic approaches are being investigated, however, a key limitation is the permeation of the blood-brain barrier. A very interesting approach is based on the use of neuro stem cells available within the brain and on the delivery of active therapeutic agents to specifically promote proliferation and differentiation. The NANOSTEM project has studied the use of nanomaterials for the delivery of active drugs to control the biological activity of neuronal stem cells. The project has focused on three main targets: (i) synthesis of the nanomaterials and uploading of the therapeutics; (ii) evaluation of the permeation and efficacy of the formulations against in vitro model systems; (iii) in vivo studies to assess the toxicity of the most successful formulations.
The project brought together six academic partners, one hospital and two industrial teams as full partners, complemented by four associate partners, one of which is an industrial team, distributed over a total of seven European Union member states. The consortium has allowed the connection of groups with very interdisciplinary expertise ranging from nanoparticle synthesis and characterization, computational modelling, in vitro Blood Brain Barrier (BBB) models and BBB transport, neural stem cells, animal testing and clinical expertise.

The project was organised into three scientific work packages:
WP1 - Synthesis and characterisation of novel nanomaterials The main objective of WP1 was to develop advanced nanostructure materials with the ability to transport drugs across the BBB, targeting the Neural stem cells.
WP2 - Permeation and bioactivity studies. WP2 focused on the development of in vitro human BBB models to screen formulations, in both healthy and diseased settings.
WP3 - In vivo evaluation of nano-delivery systems(QMUL, CNC, KI, CHUC, HMGU). This last work package aimed to (i) target and control the activity of neural stem cells, and (ii) demonstrate the effect of inductive platforms in vivo.

The work being done by the Teams belonging to the Nanostem consortium has targetted a very important scientific question related to understanding how nanoparticles may have the potential to overcome the current problems of permeating the blood-brain barrier. The results of the work have been published in peer-reviewed journals and more results will become public in the next few months.
NANOSTEM recruited 14 ESRs that were trained in areas including organic and polymer chemistry, cell biology, pharmacology, neuroscience, nanobiotechnology and clinical sciences. The project provided an extensive training program in complementary skills, targeting both professional and personal development, and translation of research and entrepreneurship. The project delivered a total of 7 Network events, including an induction course at the beginning, three summer schools and international meetings, one joint training school with the NanoCarb ETN, one clinical workshop on the impact of the blood brain barriers in the clinics and an end of Network meeting. All the 14 ESRs participated to all the events and actively engaged with the external participants. In addition the Consortium organised a NANOSTEM dedicated session at the ESB2021 Conference on Biomaterials (September 2021 that was held online, where all the ESRs delivered a scientific oral presentation.

The project achieved all its scientific deliverables, focused on the preparation of the different types of nanomaterials and also on the development of in vitro models for the blood-brain barrier, as well as collecting data on in vivo toxicity and BBB permeation. The Consortium was successful and the results have so far led to a total of 18 papers, all published in high quality journals, all open access under the gold route.
All the NANOSTEM fellows have engaged in outreach activities. For example, the ERSs actively took part to events like "Science at the Cathedral", "Science is Wonderful", "European Researchers Night", amongst many others, reaching out to hundreds of people of all ages. Unfortunately, some activities were cancelled because of COVID 19 pandemic. For example, ESRs 1, 2, and 14 were scheduled to take part to the "Big Bang Fair" in Birmingham (11th - 14th March 2020), but this event was cancelled as well as the "6th Walk for stroke of the national stroke patient day" scheduled to take place in Coimbra on the 28th of March, 2020 (ESRs 5, 6, 7, and 10).

The fellows have attended a total of 36 conferences, workshops and other meetings, a lot of which were organised as virtual events. When possible the fellows attended in person, especially when it was not requiring international travel.
The NANOSTEM website was created at the start of the project ( and has been successful as a dissemination vehicle The newsletter, created every 4 months is also uploaded on the website and widely available.
All the NANOSTEM teams engaged in research that has brought considerable progress beyond the state of the art. A number of novel nanomaterials have been prepared and characterised, and important work on understanding the interactions of such materials with biomolecules, which is essential for in-vivo applications, has been done and reported. Data on protein corona formation obtained using a combination of different techniques will enhance the understanding and also prediction of bioavailability of these particles. Some of the preparations have been evaluated in vitro together with initial studies on permeation of the blood-brain barrier model. It is expected that the large amount of data will be further evaluated and published after the end of the project, leading to further impact.
The project has focused on research that is still in its fundamental stage, therefore the most significant socio-economic impact will be in the form of new discoveries that will be further exploited by the beneficiaries. The team based at the hospital of the University of Coimbra has carried out really important work looking at data already available in the literature to establish key parameters for the evaluation of stroke patients and this could present a positive impact in clinical practice.
The fellows of the Network have been very active and fully engaged with a large number of outreach events. These have resulted in the dissemination of the work and on the education of the general public on the issues, associated with neurodegenerative diseases and their therapeutic challenges, as a result of the presence of the blood brain barrier.
The multidisciplinary training provided by the Network has contributed to the development of researchers that will be fully equipped to work in this key area of science.
NANOSTEM Group photo