CE18 - Innovation biomédicale

Bio-inspired, bioengineered and biomimetic T-cell-conjugated polymer vesicles: a biohybrid concept combining cell therapy and drug delivery carrier – TEPEE

Submission summary

The main objective of the multidisciplinary TEPEE project concerns the design of “hybrid” systems that combine the most advanced and promising developments in nanomedicine and cell therapy. As such, custom-made functional polymersomes (polymer vesicles/microcapsules) will be covalently conjugated to lymphocytes (gd T cells) in order to increase their accumulation in specific organs that are infected by the Cytomegalovirus virus (CMV). This virus is particularly resistant with a high morbidity in the context of organ transplantations. The Immuno ConcEpT team has elucidated the role of gd T cells with respect to CMV infection, and has the capability to isolate and culture them, not only in a murine model, which offers a proof-of-principle demonstrator in animals, but also in in a human model which allows validation of the concept with a realistic translational character. The LCPO and ISM teams have developed polymersomes that, while highly stable and impermeable, are able to rupture and release their content in a controlled manner in terms of time, space and wavelength as a response to a photo-induced osmotic imbalance. The global objective of the TEPEE project is to develop drug delivery systems that under a simple photo-irradiation will allow the release of an active therapeutic in a controlled fashion. Building on preliminary demonstrators, molecules which can be photocleaved efficiently using light at longer wavelengths (i.e. near-IR) that are compatible with the envisaged in vivo experiments will be further developed during the project, in order to allow the unprecedented use of this mode of activated cargo release in a biomedical application. In the current case, the liberation of the antiviral ganciclovir is of particular interest, as the bioavailability is low and the secondary side-effects are serious. Combining the expertise of the three partners, lymphocytes (gd T cells) will be used as “Trojan horses” to guide and concentrate the conjugated polymersomes in close proximity to organs infected by the CMV virus. The cell-polymersome conjugates will be tracked by fluorescence using NIR-fluorophores integrated into the functional polymersome architectures. The polymersomes will be activated through specific irradiation, in terms of wavelength, time and space, leading to the release of ganciclovir with high precision, minimising the serious side- effects associated with non-targeted drug administration. The original combination of the different experimental approaches, promises significant developments at the interfaces of cell biology, photochemistry/photophysics, macromolecular design and self-assembly, allowing the development of a breakthrough technology in the field of drug delivery. Unique training of early stage researchers will be assured, as well as efficient exchange and materials development, by the close proximity of the Bordeaux partners. Through TEPEE, the proof of concept will be established on the CMV model, but importantly, this innovative medical approach can subsequently be further generalized and applied to a range of other diseases implying a major role of lymphocytes.

Project coordination

Sébastien LECOMMANDOUX (LABORATOIRE DE CHIMIE DES POLYMERES ORGANIQUES)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LCPO LABORATOIRE DE CHIMIE DES POLYMERES ORGANIQUES
ImmunoConcEpT Immunologie Conceptuelle, Expérimentale et Translationnelle
ISM INSTITUT DES SCIENCES MOLECULAIRES

Help of the ANR 620,139 euros
Beginning and duration of the scientific project: March 2020 - 48 Months

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