SPeNTa-Brain · Synthetic Peptidic Nanovesicles for Targeting Paediatric Brain tumours
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-04-01 → 2021-12-31
- EU contribution
- €183,455
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Synthetic Peptidic Nanovesicles for Targeting Paediatric Brain tumours
In this project, we aim to get closer to a solution for the devastating disease of brain cancer, especially for children with incurable brain tumours and lifespans of few months. Paediatric glioma are the leading cause of cancer-related death in children. The limitations: Brain tumours are difficult to treat because of the special structure of our brain, that does not allow the passage and diffusion of most common anticancer drugs to reach the tumour. The brain is guarded by several barriers, with the most important and largest one the blood-brain barrier (BBB). In addition, gliomas are not defined lesions but they spread out within the brain, colonising several areas. This makes them extremely difficult to remove surgically and almost inaccessible to chemotherapy. Radiotherapy is the only option, although with severe side effects. Paediatric gliomas have a very poor prognosis and do not respond or frequently develop chemoresistance mechanisms to temozolomide (TMZ), one of the fewest drugs that crosses the BBB. Thus, there is an urgent need to develop innovative therapies, capable of reaching the brain and the tumours in a non-invasive way. To improve quality of these patients and to solve this burden, we propose here the use of nanomedicines as a non-invasive approach to treat brain cancer. Taking into account the progress made in nanomedicines design and the lessons learned from previous failures in clinical trials, we here design a new generation of super-selective nanomedicines that might represent the future of modern medicine allowing us to precisely target disease sites to improve efficacy and reduce side effects. Once validated, the versatility of this technology and concepts will allow its extension to the treatment of different solid tumours or even other CNS disorders (as versatile brain delivery system). We aim to combine different innovative concepts: (i)designing biodegradable polymersomes for brain delivery increasing the safety, avoiding unwanted accumulations; (ii)state-of the art equipment for characterization with a view for industrial development and translation of the technology; (iii) a novel TEM unit, to visualise the morphological characteristics of the polymersomes; (iv) super-selective binding that enables the specific targeting of tumour cells; (v) Combination therapy aiming to overcome chemo-resistance and seeking for synergy. Finally, the use of nanomedicines allows for personalized medicine, what means a paradigm shift in conventional treatments.
Data: CORDIS, © European Union
Project objective
Brain tumours are the most common solid tumours in children, accounting for about 25% of all primary paediatric tumours. The situation is particularly critical for the deadliest brain tumour: glioma, being the leading cause of cancer-related death in children. The main bottleneck for the treatment of central nervous system (CNS) pathologies, including brain tumours (at early stages), as well as brain metastases, lies in the difficulty to cross the blood brain barrier (BBB). In this proposal, I aim to overcome such limitation with the use of super-selective targeted and fully biodegradable polypeptide-based polymersomes, carrying relevant drug combinations for the treatment of paediatric glioma. I propose a step-wise and bottom-up approach to synthesise biodegradable polymersomes from amphiphilic block-polypeptides obtained via the scalable and reproducible methodology of Ring Opening Polymerisation (ROP) of N-Carboxyanhydrides (NCAs). The polypeptide amphiphiles are expected to self-assemble in aqueous solutions yielding nanometric vesicles. These synthetic vesicles will be functionalised with selected BBB receptor ligands in order to approach the super-selectivity concept aiming for active targeting and transcytosis to the brain acting as the so-called “Trojan Horses”. Finally, the super-selective nanovesicles will be loaded with synergistic and clinically relevant combination therapy using anticancer agents and immuno-modulators in order to approach paediatric glioma treatment. I will join for the first time, the use of fully biodegradable polymersomes based on polypeptides, super-selective binding strategies for BBB crossing and the use of chemotherapy+ immunotherapy. Overall, I will develop an innovative therapy, capable of reaching the brain in a non-invasive way, being able to diffuse and target the brain tumour, overcome chemo-resistance and activate the immune system to fight these tumours, being the future end-users, children with incurable cancers.
Original text from CORDIS.
Participants
- UNIVERSITY COLLEGE LONDON · LondonCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union