Ultra-small Nanohybrides for Advanced Theranostics

Informations projet

UNAT

N° de convention de subvention: 101008159

DOI

10.3030/101008159

Projet clôturé

Date de signature de la CE 23 Octobre 2020

Date de début 1 Avril 2021

Date de fin 31 Mars 2026

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 832 600,00

Contribution de l’UE

€ 832 600,00

Coordonné par

UNIVERSITE LYON 1 CLAUDE BERNARD
France

Periodic Reporting for period 1 - UNAT (Ultra-small Nanohybrides for Advanced Theranostics)

Période du rapport: 2021-04-01 au 2024-03-31

Résumé du contexte et des objectifs généraux du projet

For some time now, research focusing on the application of nanomaterials in different areas has become a key driver of innovation. Such innovative material are even used in medicine and are progressively making their entrance in the hospital where they are being used for diagnostic and for therapy. The UNAT project is in this line and aims at a systematic interdisciplinary study of metal-carbon nanohybrides (NHs) for possible advanced theranostic applications.
Indeed, the development of NHs based on organic & inorganic moieties can synergistically or antagonistically influence functional properties of engineered nanotheranostic drugs. UNAT will develop innovative approaches to syntheses and multi-functional application of ultra-small (<10 nm) carbon-based NHs functionalized with various metal atoms for diagnostics and therapy in the filed of oncology. In particular, carbon cores of NHs will be chemically synthesized from biomasses and/or bio-wastes.
The combination of pre-clinical in-vitro & in-vivo experiments will allow us to evaluate the theranostic potential of the NHs. the UNAT project will associate an industrial partner from Greece (Bioemtech), an industrial partner from France (GLINCS), a research and innovation center from Ukraine (Science Park) and 2 academic research groups from France (UCBL) and Italy (CNR) respectively.
The uptake efficiency and localization of NHs in cells, influenced by their surface chemistry, will be detailed. Their rich physico-chemical properties enable their use as universal multi-modal (MRI, PET, X-ray, Fluorescence, Photoacoustic) in-vivo bio-imaging agents. This multimodal strategy improves visualization reliability of NHs in tumors. Various exciting electro-magnetic sources used for medical purposes will be simultaneously used for therapy of cancer tissues containing the incorporated NHs.
The strong complementary beetween the different research experiences of the partners involved in the project and a high degree of cooperative integration between them will allow a extensive and serious study of the theranostic potential of the NHs.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The UNAT project faced significant challenges due to the COVID-19 pandemic and the Russia-Ukraine war. These crises profoundly impacted the project's implementation. Despite this, the UNAT consortium managed to effectively implement the project to some extent over the first three years.The main achievements of the UNAT project over the first 3 years included:
- The kick-off meeting was successfully held online on 22th April 2021.
- The setting-up of the management legal frame, governing bodies and operating tools and launch, preparation and distribution of the required tools to ensure a smooth project management.
- The launch of the website (https://www.unat-project.eu).
- Internal and external communication templates based on the project's graphic chart have been prepared to enhance the visibility of the UNAT project. A dedicated visual identity, including a logo, website header, fonts, and colors, was also established.
- A collaborative platform has been set up to securely centralize and share project-related documents.
- In frame of the Work Package 2 (WP2), Gd3+-free and Gd3+-doped carbon-based NHs were successfully synthesized.
- As part of the WP2, NHs were produced from food industry by-products, specifically: coffee waste, chestnut, and peanut shells.
- By adjusting synthetic conditions and dispersing mediums, photophysical properties as well as potential biomedical applications of the NHs can be adjusted.
- In frame of the WP3, in vitro cytotoxicity assays demonstrated that all the NHs exhibited good biocompatibility at concentrations as high as 1 mg/mL.
- As part of the WP3, in vitro neurotoxicity tests indicated that the incorporation of Gd into the NHs did not increase their toxicity, suggesting their strong chelating properties.
- Some NHs were found to be the most tolerated in-vivo by mice after multiple doses at concentrations adequate for bioimaging and therapeutic applications.
- A request for Amendment was initiated in January 2023 aiming at integrating a new partner, Glincs and the extension of the duration of the project.
- The organisation of the first UNAT workshop within the frame of the Nanohybrid 18 conference on 30th May - 1st June 2022 in Bastia, before the project mid-term meeting with the EC officer.
- An additional workshop was organized in the frame of the Nanohybrids XIX-2023 conference from May 29 to June 02, 2023, in Porquerolles, France.
- The mid-term meeting on May 31, 2022, in cooperation with REA, assessed project implementation, progress, and challenges.
- 4 newsletters were released every six months, covering project outcomes, events, publications, and secondments.
- 9 publications were successfully submitted and made openly available.
- V. Lysenko, UNAT Coordinator, as a Guest Editor of a Special issue "Photoacoustic and Photothermal Phenomena" in Nanomaterials.
- 41 secondments, totaling 80 months, were implemented in the first reporting period.
- A project video illustrating the secondment of two Ukranian researchers at University of Lyon was produced by Deutsche Welle and is now online here: https://www.dw.com/en/ukrainian-scientists-find-refuge-in-france/av-61748596

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The UNAT consortium aims to establish lasting research collaborations and efficient knowledge transfer between European academic and non-academic partners. Each organization will continue to send researchers for advanced training and collaboration. The shared knowledge will enhance the expertise of all partners.
In parallel, the multi-disciplinary researches epitomized in the UNAT project is a major opportunity at EU level to catalyze scientific developments around nanotechnologies dedicated to cancer treatment and must enable clinical translation beyond what is currently used in hospitals. Furthermore, interdisciplinary collaboration among researchers with diverse backgrounds in chemistry, material science, biotechnology, and biomedical research will be crucial in driving innovation and translating laboratory findings into practical solutions for theranostic applications using the original bio-functionalized NHs.
A wide range of NHs with various surface functionalities was already synthesized during the first 3 years of the UNAT project. Future efforts to synthesize non-toxic and biocompatible carbon-based nanohybrides from biowaste for theranostic applications will likely focus on refining extraction techniques, optimizing synthesis processes, and exploring novel biowaste sources. There will be a concerted effort to develop sustainable and cost-effective synthesis routes, potentially utilizing green chemistry principles and renewable energy sources. Exploring a wide range of biowaste sources, including agricultural residues, food waste, and byproducts from various industries, will expand the repertoire of available CDs precursors, offering versatility and resourcefulness in synthesis approaches.
The final impact of the proposal on European/international biomedical level is expected to be quite strong: the outcome of the project migth represent new possible cancer therapy approaches based on carbon-based NHs. Overall, future endeavours in this field hold promise for harnessing biowaste as a valuable resource for sustainable and multifunctional carbon dot synthesis, advancing the frontier of theranostic nanomedicine.

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