Lartigue Lenaic
Universite de Nantes, France
Title: Ultra-bright magnetic nanoassemblies as theranostic agents
Biography
Biography: Lartigue Lenaic
Abstract
Multifunctional nanoparticles have recently emerged as promising cross-correlated contrast agents for bioimaging and carrier for drug delivery. The combination of magnetic and fluorescent units inside the same assemblies allows in vitro fluorescence microscopy (multiplexing, sensitivity and high resolution) and in vivo magnetic resonance imaging (MRI) (no penetration limit) with the same nanotools. We report a one-step synthesis to prepare core-shell architectures displaying a high payload of self-assembled magnetic and fluorescent units for improved multimodal tracking. This innovative architecture could contain drug agents for on-demand drug delivery. The multifunctional nanoparticles displayed a core-shell structure. The core consists an ultra-bright fluorescent organic nanoparticle (brightness>107 mol-1Lcm-1) tightly coated with superparamagnetic iron oxide nanoparticles, known as highly sensitive MRI contrast agents. The closely packed magnetic nanoparticles create strong additivity at the surface (r2=250 s-1mmol-1L), so that large MRI T2 contrast was obtained with unusually diluted solutions in vitro or after intravenous injection in small rodents. Two-photon excited fluorescence imaging could be performed, achieving unprecedented location resolution for agents combining both magnetic nanoparticles and fluorescence properties. Post-functionalization is ensured through an anionic polymer which is readily tailored to ensure furtivity (PEG chain) or active targeting (biotin, protein, etc.) via surface bioconjugation. In vitro studies show the importance of the polymer nature on the kinetics of cellular uptake. In vitro studies are performed on various cells and demonstrated the non-toxicity of our systems. Endocytosis kinetics was elucidated in mesothelium cancer cells grown as monolayers or multicellular tumor cell spheroids. Compared to numerous architectures like polymersomes or liposomes, the reported innovative nanoassemblies display in vitro a very high structural cohesion. The high density of magnetic nanoparticles leads to cooperative dipole effects, so that straightforward comparative investigations at various scales can be achieved using two-photon excited fluorescence imaging and in vivo magnetic resonance imaging (MRI).