Biointeractions at the nanointerface

Topic description

Despite profuse literature and promising results, very few nanomedicines have been successfully translated to the clinic. For some years now, the poor understanding of the mechanisms controlling the circulation time of nanoparticles (NPs) in the blood stream has been identified as a major obstacle to nanomedicine development.1 Indeed, interactions between NPs and the cells forming the reticulo endothelial system (RES) are known to dictate how fast NP are cleared for blood and these interactions are suspected to be strongly dependent on the surface properties of the particles and on their interaction with proteins.2

The goal of the project is to elucidate the role of surface chemistry and the protein corona forming on NPs, on the pharmacokinetics of NPs in vivo. Various strategies will be explored to characterize NPs interactions with the RES and in vivo. In vitro, large libraries of NPs suspensions with controlled surface chemistry will be produced using automated high throughput microfluidic nanoprecipitation. To create large enough chemical diversity, diblock polymers will be used as building blocks of the NPs formed by self-assembly. Screening of interaction profiles of the generated NP library will be assessed in vitro on 3D organoids and in vivo on small animal models. Analysis of structure – property relationships will be performed using state of the art Deep learning algorithms.

The knowledge generated during this project will advance our comprehension of nanomaterials interactions with living matter and will help design novel drug delivery systems with improved biodistribution and pharmacokinetic profiles.

The PhD student will join Pr Xavier Banquy’s laboratory, at the Faculty of Pharmacy, whose expertise spans from polymer synthesis and production of NPs, drug delivery, microfabrication and advanced imaging. The multidisciplinary nature of the project will require interaction with multiple research teams within and outside the group.

1. Dai, Q. et al. Quantifying the Ligand-Coated Nanoparticle Delivery to Cancer Cells in Solid Tumors. ACS Nano 12, – .

2. Blanco, E. et al. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology 33, – .

Starting date

-09-01

Funding category

Public/private mixed funding

Funding further details

Approved for the duration of the PhD