ExoBBB · Design and development of exosomes with brush type architecture as RNA delivery vectors for active targeting of blood brain barrier (BBB)
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2022-05-01 → 2024-04-30
- EU contribution
- €159,815
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Design and development of exosomes with brush type architecture as RNA delivery vectors for active targeting of blood brain barrier (BBB)
Small extracellular vesicles (sEVs) also known as exosomes are nanosized vesicles which are secreted by cells. These nanosized vesicles are naturally enriched with a pool of therapeutic molecules such as proteins, microRNAs (miRNAs) etc. Hence delivery of these sEVs to human body compartments is a promising approach to tackle several diseases such as cancer, chronic wounds, neurological disorders etc. But sEV delivery to the blood circulation faces several challenges. One of the biggest challenge is their very short lifetime in the blood circulation. These sEVs are rapidly cleared from the blood circulation by our body's natural defence mechanism which in turn will result in less accumulation of the sEVs in target organs such as heart, lungs, brain etc. Less accumulation of the sEVs in target organs will ultimately result in poor therapeutic efficacy. Considering the above said challenges, it is very important to do research in designing exosomes with properties to overcome the rapid elimination from blood circulation and also to accumulate significantly in target organs. The project ExoBBB aimed to solve the above said challenges by modulating the physicochemical properties of exosomes thereby enabling them to perform as more efficient therapeutic carriers. Physicochemical properties of exosomes were modulated by growing polymers in the form of brushes (polymer brushes) from the surface of exosomes using polymerization techniques. Overall objectives of ExoBBB were 1) isolate, purify and characterize small extracellular vesicles or exosomes 2) Modulate the physicochemical properties of these exosomes using polymer brushes 3) Characterize the developed exosome-polymer brush hybrids 4) Assess the impact of various exosome-polymer brush hybrids on cells 5) Evaluate the behaviour of these exosome-polymer brush hybrids after administering to blood circulation of small animals We have used a combinatorial approach to develop a series of exosome-polymer brush hybrids , characterized them and evaluated their interactions with cells and their behaviour after entering the blood circulation of mice. From the results generated, we could identify some exosome-polymer brush hybrids with significantly higher retention time in the blood circulation of mice.
Data: CORDIS, © European Union
Project objective
MicroRNAs (miRs) are identified as significant regulators in modulating brain functions in central nervous system (CNS) disorders like Alzheimer’s disease (AD), Huntington’s and Parkinson’s disease (PD) and amyotropic lateral sclerosis. Sustained delivery of miRNAs to brain could be an excellent strategy to regulate gene expressions affected in the progressive neurodegenerative diseases. Highly biocompatible nanocarriers like extracellular vesicles (eg: exosomes) are an excellent choice as delivery vehicles for miRs but their short half life in systemic circulation and difficulty in crossing BBB limits the application. ExoBBB proposes to use high density polymer brushes to maximise RNA capture and stability, confer biofunctionality, stealth behaviour and active targeting to CNS. Density and chemical composition of these polymer brushes can be tuned precisely to attain optimum physicochemical features necessary for active targeting of BBB. Grafting of polymer brushes over exosomes can impart a star shaped architecture which in turn has been proven effective for neuronal targeting. In addition, these brushes can offer abundant surface functionalities for the conjugation of active targeting ligands. Dual targeting ability of the polymer brush chains will be evaluated by surface modification with peptides which can actively target BBB and neurons. The aim of ExoBBB is to design highly stable and efficient cationic polymer brush-based RNA delivery vectors that can be grafted on safe and biocompatible nanoparticles like exosomes for brain targeting and regulation of neuronal cell phenotype for prolonged periods of time.
Original text from CORDIS.
Participants
- CENTRO DE NEUROCIENCIAS E BIOLOGIACELULAR ASSOCIACAO · COIMBRACoordinatorPortugal
Links
Data: CORDIS, © European Union