Nanomédecine et administration de nanovecteurs par voie muqueuse
The NANOVEC group aims at understanding mucosal biology and develops nanovectors to improve mucosal uptake of vaccines and biotherapies.
Axis 1: Role of the microenvironment in cell plasticity in mucosal tissues. PI: Nicolas Aznar
The microenvironment influences cell fate, promoting regeneration and repair under physiological conditions. However, in pathological contexts such as chronic inflammatory diseases, the microenvironment can be co-opted to support treatment resistance. To fully understand how the microenvironment drives complex processes, advanced models that accurately mimic human tissue behavior are essential. Organoid technology provides a robust platform to study cellular plasticity in a controlled, three-dimensional environment. These organoid models are not only invaluable for basic research but also offer promising opportunities for developing innovative nanovectors and study their penetration and influence on 3D mucosal models. In response to the growing need for access to organoid technology, we established the 3D BIO Organoid Facility at the SFR Biosciences.
Axis 2 – Mucopenetration strategies, targeting and biodistribution. PI: S. Richard
This research axix aims at understanding and identifing the mechanisms involved in the uptake of nanovectors across biological barriers, particularly mucous membranes, in order to improve their passage and optimize their biodistribution. To achieve this objective, we implement approaches to improve the mucopenetration of these vectors, developing specific targeting strategies and exploiting advanced imaging tools. In many studies, the efficacy of nanomedecines is assessed solely on the basis of their biological activity, without considering their trajectory or localisation after administration. This limitation is largely due to the lack of suitable tools for studying the precise fate of these nano-objects. We are convinced that current scientific questions remain unsolved due to technological issues that could be overcome by our integrated nanotechnology approaches that uses the same vehicle for biodistribution studies and therapeutic delivery. This theme proposes to develop mucopenetrant nanoparticles as multimodal platforms for in vivo imaging.
Axis 3 – Design of nanovectors and study of immunostimulation. PI: Danielle C. Arruda
The main objective of this axis is to explore strategies for inducing mucosal immune responses through mRNA vaccination using lipids, polymers, and/or hybrid nanoparticles as non-viral vectors. First, nanoparticles composed of mRNA and adjuvants are formulated using automated microfluidic systems to fine-tune their physicochemical properties for crossing the mucosal barrier. Second, the mechanisms of nanoparticle uptake and the efficiency of mRNA expression, as well as the immune pathways they activate, are investigated using in vitro/ex vivo models. Finally, the antigen-specific immune response, with a focus on secretory antibodies and tissue memory responses, are analyzed following in vivo mucosal immunization with selected mRNA-based nanovaccines encoding a model or clinically relevant antigen, as a proof-of-concept for vaccination.
Axis 4 – Mucosal immune response during aging. PI: Claire Monge
Even during healthy aging, the functions of the immune system may be weakened by a process known as immunosenescence and inflammaging that are responsible for the increasing incidence of infections in the population over 65. Elderly population also show weaker responses to vaccination than younger one, mainly due to age-associated changes in the primary and secondary lymphoid organs, and mofifications in the activation of the immune response. This axis is based exploration of the influence of the aging of the mucosal tissue itself during mucosal vaccination of old to geriatric mice models and investigated new adjuvant strategies to overcome inflammaging and restore a robust vaccine response in elderly individuals.
Claire Monge, chercheuse en biotechnologie | Talents CNRS | Médaille de bronze 2023
Thèmes
• Administration et immunité muqueuses
• Prise en charge in vivo de nanovecteurs particulaires et ciblage thérapeutique
• Vaccins nanoparticulaires et réponses immunitaires
• Hydrogels bioactifs et biomatériaux thérapeutiques
• Adaptation cellulaire et thérapies de l’elasticité
Mots-clés : nanovecteurs, nanomatériaux, polymères biodégradables, hydrogels, biomatériau, vaccins, adjuvants, muqueuses, biodistribution
Membres : Équipe Vecteurs colloïdaux et ingénierie thérapeutique ciblée
Publications : Publications Vecteurs colloïdaux et ingénierie thérapeutique ciblée
Contact
Equipe NANOVEC
Laboratoire de Biologie Tissulaire et Ingénierie thérapeutique – CNRS – UMR 5305 – Université Claude Bernard Lyon 1
Institut de Biologie et Chimie des Protéines
7, passage du Vercors 69367 LYON CEDEX 07
FRANCE
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