Nano-Biological Contrast Agent Platform for MRI Imaging

Project Information

Nano-imaging

Grant agreement ID: 101069356

DOI

10.3030/101069356

Project closed

EC signature date 30 May 2022

Start date 1 October 2022

End date 31 March 2024

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

ASOCIACION CENTRO DE INVESTIGACION COOPERATIVA EN BIOMATERIALES- CIC biomaGUNE
Spain

Periodic Reporting for period 1 - Nano-imaging (Nano-Biological Contrast Agent Platform for MRI Imaging)

Reporting period: 2022-10-01 to 2024-03-31

Summary of the context and overall objectives of the project

NANO-IMAGING proposes the elucidation of the potential of a novel metal-protein hybrid nanostructure as a platform for the development of organ-specific Magnetic Resonance Imaging (MRI) contrast agents. This proposal builds on the large demand for MRI examinations worldwide, the health concerns raised by available contrast agents, and the little choice of tissue-specific contrast agents available to clinical practitioners. The unique value proposition of NANO-IMAGING —a safe, bright, and tissue-specific MRI contrast agent— is possible due to the purposely designed structure and composition of the nanostructure and tissue-targeting properties thereof.

The proposed solution, based on proprietary technology, allows for the control of the nanomaterial properties and the straightforward customization of targeting moieties. Having observed the basic principles of the technology; formulated the concept behind the idea; and made in-vitro experiments that prove the consistency of our revolutionary approach, now we want to further the technology towards the clinical practice by testing the technology in-vivo.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The research activities have been mostly focused on the development of the three main objectives of the Nano-Imaging project:

Objective 1. Technological development and fabrication of a MVP: NANO-IMAGING accomplished the creation of a collection of protein-nanomaterial hybrids with good imaging properties, comparable to commercially available contrast agents. The imaging properties could be tuned by the protein construct and synthesis methods. The contrast agent-stabilizing capabilities of the systems are expected to be orthogonal to the biological activity of the targeting moieties. Additionally, the newly developed contrast agents exhibited good imaging properties in cells and stability in biological media, making them promising agents for in vivo applications.

Objective 2. Validation of MVP and platform technology, and competitive analysis: we accomplished a collection of protein-nanomaterial hybrids validated in in-vitro systems. The protein-nanomaterial modules were fused to diverse targeting agents specific to different molecules, demonstrating the modularity and versatility of the system. With this approach, we originated orthogonal multifunctional systems with the metal nanocluster coordination and biological binding functions being simultaneously encoded in the same protein scaffold. Engineered proteins were leveraged as scaffolds for the design of proteins with binding motifs against various biologically relevant targets. In particular, two systems were developed against cancer-related protein biomarkers. In addition, the protein scaffold offered a platform rich in chemically reactive groups, facilitating the straightforward conjugation of functional agents—in this case, alendronate, targeting calcifications in atherosclerotic plaques. The resulting protein-nanomaterial hybrids were robust enough to endure intravenous injection in mice and accumulated at target sites, enabling in-vivo diagnosis.

Objective 3. Market Potential Assessment: The technology is patent-protected in international markets. Key Opinion Leaders (KOL) on contrast agent development that could validate the Nanoimaging Platform were identified and interviewed. The main goal of this task was to gain an understanding of the needs, challenges and opportunities in the area of organ-specific contrast agents in particular−for MRI. The interviews with KOLs allowed identifying key areas for innovation, as well as understanding the factors that influence the adoption of new technologies in clinical practice. All the markets where NANO-IMAGING can be positioned are expected to grow in the forecast period with a compound annual growth rate (CAGR) value of approximately between 2 and 7 %. The Contrast Media Market is estimated to be worth USD8.7 B, the Magnetic Resonance Imaging Contrast Media Market is estimated to be worth USD3.4 B and the Global Atherosclerosis Market is estimated to be worth USD17 B.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The NANO-IMAGING project has achieved significant advancements in the field of targeted contrasts agents, surpassing the current state of the art in multiple aspects. Here we highlight the potential impacts of these results and the key needs for development thereof.
The project has demonstrated the feasibility of protein-nanomaterial hybrids as versatile MRI contrast agents. However, to enhance their effectiveness, further research will be needed mainly to explore alternative metal coordination compounds with improved imaging properties and conducting advanced simulations using the developed nanomaterial datasets to predict the performance, and design advanced contrast agents for MRI.

Reported demonstrations have shown positive in-vivo results, particularly in targeting calcifications in atherosclerotic plaques. Future demonstrations should focus on additional applications, such as fibrosis, cancer, and neurodiseases. Some of these efforts are already in progress, aiming to expand the clinical utility of the developed contrast agents.
The project has initiated the combination of contrast agents with therapeutic molecules based on the same scaffolds, paving the way for new theranostic applications. This combination approach enhances the potential for targeted therapy and diagnosis within a single platform, representing a significant advance in the integration of diagnostics and therapeutics.
To extend the scope of NANO-IMAGING beyond current collaborations, the project aims to establish partnerships with additional international stakeholders to facilitate further development of the technology, ensuring broader impact and potential market application.
For the successful development and commercialization of NANO-IMAGING technology, the creation of a spin-off company in late 2025 is envisioned. Alternative strategies such as licencing of the technology to other companies will also be considered. The potential spin-off will be supported by a comprehensive business plan, including detailed financial strategies and funding approaches, and a regulatory framework to ensure sustainable growth and market entry.

Overall, NANO-IMAGING has achieved groundbreaking advancements in the development of tissue-specific MRI contrast agents by combining innovative protein engineering with metal coordination chemistry. The project successfully produced protein-nanomaterial hybrids with excellent imaging properties comparable to commercially available contrast agents. Moreover, they exhibit advantageous biocompatibility and stability, while showing specific targeting capabilities, as illustrated by the successful imaging of atheroma plaques in vivo. The project has further validated the technology both in vitro and in vivo, demonstrating its modularity and versatility through the fusion of protein-nanomaterial modules with various targeting agents. In-vivo experiments showed the robustness and targeting capability of these hybrids and thus their potential for clinical applications and versatility. Finally, NANO-IMAGING conducted a comprehensive market assessment, identifying key opinion leaders and growth opportunities in the MRI contrast media market, especially within the atherosclerosis market, illustrating the significant commercial potential for NANO-IMAGING.