DS0411 -

Functionalized NANOparticular Polysaccharidic Agents for spectral Computed Tomography for molecular imaging of atherothrombosis – NANOPACT

Submission summary

NANOPACT (functionalized NANOparticular Polysaccharidic Agents for spectral Computed Tomography) is a collaborative project between three academic laboratories and two companies, Algues & Mer, who extracts from seaweeds active ingredients mostly for cosmetics and nutraceutics, and Toshiba Medical France, who develops post-processing tools for the analysis of spectral Computed Tomography (CT) imaging.

This project fits into the fight against cardiovascular diseases by developing a novel and biospecific Polysaccharide-Based Nanoparticles (PBN) sensitive to X-ray and functionalized with fucoidan for targeting P-selectin on activated platelets for the molecular imaging of atherothrombosis with spectral CT imaging.

The strategy is based on the use of fucoidan, a marine polysaccharide able to specifically bind to P-selectin, which is a well-established marker of thrombosis. Imaging is based on the routinely used X-ray contrast agents, namely iodine and gadolinium (Gd) that can be easily and specifically be identified on spectral CT imaging due to the unique signature of their attenuation curve. The stability of the whole nanoconstruct is achieved with polysaccharides, giving functionalized PBN contrast agents sensitive to X-ray.

The novelty with NANOPACT project is the synthesis of biospecific nanoparticles offering the advantages of both improved haemocompatibility and reduced lateral toxicity due to the exclusively polysaccharidic nature of the nanosystems. Three polysaccharides will be used: amylose (3 different origins), carboxymethyldextran (CMD) and fucoidan (4 molecular weight fractions of 80 to 200 kDa) the latter being already validated for molecular imaging of atherothrombosis with other imaging modalities such as MRI and SPECT. The polysaccharides will be carriers of iodine and gadolinium, which serve as X-ray contrast agents for spectral CT imaging.

The main objectives of NANOPACT are:
1. Preparation of fucoidan fractions with different molecular weight from a commercial fucoidan.
2. Preparation of various PBN and their coating with fucoidan.
3. Functional analysis of fucoidan-bearing PBN by in vitro assays to assess their targeting capacity and evaluation of cytotoxicity on human vascular cells and peripheral blood mononuclear cells.
4. Validation in experimental animals models of atherothrombosis with spectral CT imaging and selection of the best fucoidan-bearing PBN for industrial development.

A multidisciplinary consortium including chemists, physico-chemists, biologists, radiologists and industrial experts in state-of-the-art spectral CT imaging in small animals and Human, will synthesize the fucoidan-bearing PBN and evaluate their potential for diagnosis. This original strategy based on well-grounded principles and systems has a high potential for industrial transfer and by addressing a major medical need can have a large impact on healthcare.

Project coordination

Phalla OU (Laboratory for Vascular Translational Science)

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

ALGUES ET MER
TOSHIBA MEDICAL France
CREATIS Centre for Research and Applications in Image and Signal Processing
LVTS Laboratory for Vascular Translational Science
PBS Laboratoire Polymères, Biopolymères et Surfaces

Help of the ANR 442,158 euros
Beginning and duration of the scientific project: March 2017 - 48 Months

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