Objectives

METRINO aims to develop traceable measurement methods for the characterisation of innovative nanotherapeutics and associated RM candidates, focusing on synthetic lipid-based nanoparticles, e.g., liposomes and LNPs-RNA, and MONPs. The specific objectives are to:

1. Develop RM candidates for synthetic lipid-based and metal oxide nanoparticles and to measure their chemical composition, particle size distribution, polydispersity and particle concentration with a controlled uncertainty using existing methods (WP1)
2. Develop and harmonise traceable methodologies for measuring: a) particle size and concentration of small (<10 nm) nanoparticles and agglomerated or aggregated non-spherical objects, b) lipid composition and structural integrity of lipid-based nanoparticles, and c) nanoparticle surface properties, including the amount, chemical composition, and homogeneity of the surface coating (WP2)
3. Develop and harmonise robust and efficient sample preparation methods for the measurements of the nanoparticle stability and their biotransformation in biological matrices, and to minimise matrix interferences. Fractionation methods will be used, including size exclusion chromatography (SEC), field flow fractionation (AF4) and ultracentrifugation (UC) that are used to separate nanoparticles from free proteins in plasma (WP3);
4. Improve correlative methods and model tissue phantoms to measure nanoparticle uptake and distribution in single cells and tissues associated to their biodistribution profile, safety, and efficacy. This includes using a combination of complementary techniques (e.g., MS, single cell ICP-MS, EM, Raman- and fluorescence-based approaches) with the aim to reduce the uncertainty in the detection, localization, and quantification of nanoparticles in single cells and tissues (WP4).
5. Facilitate the take up of the technology and measurement infrastructure developed in the project by the measurement supply chain (NMIs, accredited laboratories), standards developing organisations (e.g., CEN/TC 352-Nanotechnologies, ASTM E56, ISO TC 229), VAMAS TWA 2 and TWA 34 and end users (e.g., the pharmaceutical industry, regulators, clinicians, nanomedical product manufacturers, nanomedicine research community) (WP5).