Intracellular Delivery by Out-of-Equilibrium FoldAmers – IDEA

The effective and safe intracellular delivery of new pharmaceutical ingredients represent a major hurdle in the translation of biomedical discoveries to applications in the clinic. Cell-penetrating peptides are promising vectors but critical issues such as lack of selectivity and systemic toxicity have hampered their clinical application. To solve this challenge, we propose in this research project the design of an addressable vector that can be selectively activated when pushed out-of-equilibrium – with resolution in space and time – to transiently trigger cell penetration before degrading and releasing the free drug. The trigger we selected is visible light as it is benign and can nowadays be used in the clinic thanks to recent developments in biooptic technologies, and the activity switch rests on a change of conformation and involves the transient folding of the vector. The IDEA project has a two-fold ambition to i) unveil a new family of molecular objects that transiently fold upon light irradiation, and, through this basic discovery, to ii) provide a new, original and usable solution for drug delivery.