Akhilesh Rai

University of Coimbra, Portugal

Title: Peptide decorated light-responsive nanoparticles for the brain targeting

---

Biography

Akhilesh Rai is a FCT assistant Investigator at Faculty of Medicine, University of Coimbra from 2017. Previously, he was an assistant Investigator at Center for Neuroscience and Cell Biology (CNC), University of Coimbra from 2013 to 2017. He has been involved in several European Union projects.  He has more than 15 years of experience in the area of nanomaterials, antimicrobial nanoformulations and the application of nanoparticles in drug delivery applications. I am recognized expert in area of nanotechnology and biomaterials with more than 24 publications, 2 book chapters and 1 patent. Our work related to antimicrobial nanoparticles have been recognized and I have been conferred the prestigious Bluepharma-University of Coimbra Innovation award (2015) for the project Bug-killer. I was a co-founder of Spin-off Company “CureMat technologies”, which had focused on development of peptide-NP based wound dressings. 

Abstract

Stimulation of adult neurogenesis by targeting the endogenous neural stem cells, located in hippocampus and subventricular zone (SVZ), has been proposed for brain repair in cases of neurodegenerative diseases [1]. One major drawback for the treatment of these diseases is the incapacity of drugs/carriers to cross efficiently the BBB [2]. Studies have demonstrated that nanoparticles (NPs), upon a intracerebroventricular administration, can deliver active molecules at the SVZ region, triggering the neurogenic process [3]. Nevertheless, this type of administration is very invasive and requires specific medical facilities, which lead to an increase interest in the identification of strategies to administer the NPs by intravenous route. So far, it is relatively unknown the required properties to facilitate NPs accumulation in the neurogenic niches.

Here, we have screened gold nanoparticle (AuNPs) formulations having variable morphology (spherical and rod shape), surface chemistry [different density of transferrin (Tf) peptide] and responsiveness to light for their capacity to cross the BBB and accumulate preferentially in the neurogenic niches. Results obtained in a human in vitro BBB model showed that AuNPs and gold nanorods (AuNRs) conjugated with Tf peptides between 169 and 230 crossed more efficiently than formulations with higher or lower peptide number per formulation, without affecting the barrier properties. The transcytosis of Tf conjugated AuNPs and AuNRs depend on avidity of Tf receptors with different densities of Tf peptide. We further show that AuNRs conjugated with Tf, administered intravenously in mice and activated by a near infrared light, had the highest accumulation in SVZ, due to a transient opening of the BBB probably induced by local heat. In summary, we show that controlling the properties of NPs formulations we can target more effectively the neurogenic niches, opening new possibilities for brain regeneration.