Nanoparticles produced by ring-opening metathesis polymerization using norbornenyl-poly(ethylene oxide) as a ligand-free generic platform for highly selective in vivo tumor targeting

We described a norbornenyl-poly(ethylene oxide) nanoparticles ligand-free generic platform, made fluorescent with straightforward preparation by ring-opening metathesis polymerization (ROMP). Our method allowed to easily obtain a drug delivery system (DDS) with facilitated functionalization by means of azide−alkyne click chemistry and with a high selectivity for the tumor in vivo, while cellular internalization is obtained without cell targeting strategy. We demonstrated that our nanoparticles are internalized by endocytosis and colocalized with acidic intracellular compartments in two models of aggressive tumoral cell lines with low prognostic and limited therapeutic treatments. Our nanoparticles could be of real interest to limit the toxicity and to increase the clinical benefit of drugs suffering rapid clearance and side effects and an alternative for cancers with poorly efficient therapeutic solutions by associating the drug delivery in the tumor tissue with an acid-sensitive release system.Fabien Gueugnon, Iza Denis, Daniel Pouliquen, Floraine Collette, Régis Delatouche, Valérie Héroguez, Marc Grégoire, Philippe Bertrand and Christophe Blanquar