Heparin length in the coating of extremely small iron oxide nanoparticles regulates in vivo theranostic applications.

Autor: Groult H; BCBS team (Biotechnologies et Chimie des Bioressources pour la Santé), LIENSs Laboratory (Littoral environment et Sociétés), UMR CNRS 7266, University of La Rochelle, La Rochelle, France. hugo.groult@univ-lr.fr thierry.maugard@univ-lr.fr., Carregal-Romero S; CIC biomaGUNE and Basque Research and Technology Alliance (BRTA), Donostia-San Sebastián, Gipuzkoa, Spain. jruizcabello@cicbiomagune.es and CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain., Castejón D; Unidad de RMN - CAI Bioimagen Complutense, Universidad Complutense de Madrid, Spain., Azkargorta M; Proteomics Platform CIC bioGUNE, Bizkaia Science and Technology, Derio, Spain., Miguel-Coello AB; CIC biomaGUNE and Basque Research and Technology Alliance (BRTA), Donostia-San Sebastián, Gipuzkoa, Spain. jruizcabello@cicbiomagune.es., Pulagam KR; CIC biomaGUNE and Basque Research and Technology Alliance (BRTA), Donostia-San Sebastián, Gipuzkoa, Spain. jruizcabello@cicbiomagune.es., Gómez-Vallejo V; CIC biomaGUNE and Basque Research and Technology Alliance (BRTA), Donostia-San Sebastián, Gipuzkoa, Spain. jruizcabello@cicbiomagune.es., Cousin R; BCBS team (Biotechnologies et Chimie des Bioressources pour la Santé), LIENSs Laboratory (Littoral environment et Sociétés), UMR CNRS 7266, University of La Rochelle, La Rochelle, France. hugo.groult@univ-lr.fr thierry.maugard@univ-lr.fr., Muñoz-Caffarel M; Molecular Oncology Group, Biodonostia Health Research Institute, San Sebastian, Spain and Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain., Lawrie CH; Molecular Oncology Group, Biodonostia Health Research Institute, San Sebastian, Spain and Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain., Llop J; CIC biomaGUNE and Basque Research and Technology Alliance (BRTA), Donostia-San Sebastián, Gipuzkoa, Spain. jruizcabello@cicbiomagune.es and CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain., Piot JM; BCBS team (Biotechnologies et Chimie des Bioressources pour la Santé), LIENSs Laboratory (Littoral environment et Sociétés), UMR CNRS 7266, University of La Rochelle, La Rochelle, France. hugo.groult@univ-lr.fr thierry.maugard@univ-lr.fr., Elortza F; Proteomics Platform CIC bioGUNE, Bizkaia Science and Technology, Derio, Spain., Maugard T; BCBS team (Biotechnologies et Chimie des Bioressources pour la Santé), LIENSs Laboratory (Littoral environment et Sociétés), UMR CNRS 7266, University of La Rochelle, La Rochelle, France. hugo.groult@univ-lr.fr thierry.maugard@univ-lr.fr., Ruiz-Cabello J; CIC biomaGUNE and Basque Research and Technology Alliance (BRTA), Donostia-San Sebastián, Gipuzkoa, Spain. jruizcabello@cicbiomagune.es and CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain and Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain and Departamento de Química en Ciencias Farmacéuticas, Universidad Complutense de Madrid, Madrid, Spain., Fruitier-Arnaudin I; BCBS team (Biotechnologies et Chimie des Bioressources pour la Santé), LIENSs Laboratory (Littoral environment et Sociétés), UMR CNRS 7266, University of La Rochelle, La Rochelle, France. hugo.groult@univ-lr.fr thierry.maugard@univ-lr.fr.
Jazyk: angličtina
Zdroj: Nanoscale [Nanoscale] 2021 Jan 21; Vol. 13 (2), pp. 842-861.
DOI: 10.1039/d0nr06378a
Abstrakt: The positive contrast of extremely small iron oxide nanoparticles (ESIONP) in magnetic resonance imaging (MRI) rejuvenates this class of metal nanoparticles (NP).Yet, the current synthesis often lacks the possibility of adjusting the core size (while it is a key element for ESIONP-based MRI contrast behaviour), and also involved multiple complex steps before obtaining a ready-to-use probe for medical applications. In this study, we faced these challenges by applying heparin oligosaccharides (HO) of different lengths as coatings for the preparation of HEP-ESIONP with a one-pot microwave method. We demonstrated that the HO length could control the core size during the synthesis to achieve optimal positive MRI contrast, and that HEP-ESIONP were endowed directly with anticoagulant properties and/or a specific antitumor activity, according to the HO used. Relevantly, positron emission tomography (PET)-based in vivo biodistribution study conducted with 68Ga core-doped HEP-ESIONP analogues revealed significant changes in the probe behaviours, the shortening of HO promoting a shift from hepatic to renal clearance. The different conformations of HO coatings and a thorough in vitro characterisation of the probes' protein coronas provided insight into this crucial impact of HO length on opsonization-mediated immune response and elimination. Overall, we were able to identify a precise HO length to get an ESIONP probe showing prolonged vascular lifetime and moderate accumulation in a tumor xenograft, balanced with a low uptake by non-specific organs and favourable urinary clearance. This probe met all prerequisites for advanced theranostic medical applications with a dual MRI/PET hot spot capability and potential antitumor activity.
Databáze: MEDLINE
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