ExoBBB · Design and development of exosomes with brush type architecture as RNA delivery vectors for active targeting of blood brain barrier (BBB)

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.