Characterization and biodistribution of Au nanoparticles loaded in PLGA nanocarriers using an original encapsulation process.
Fiche publication
Date publication
mai 2021
Journal
Colloids and surfaces. B, Biointerfaces
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DENAT Franck, Pr ROUX Stéphane
Tous les auteurs :
Laurent G, Benbalit C, Chrétien C, Dupuis C, Pellequer Y, Bazzi R, Thakare VS, Denat F, Roux S, Béduneau A
Lien Pubmed
Résumé
Due to their imaging and radiosensitizing properties, ultrasmall gadolinium chelate-coated gold nanoparticles (AuNP) represent a promising approach in the diagnosis and the treatment of tumors. However, their poor pharmacokinetic profile, especially their rapid renal clearance prevents from an efficient exploitation of their potential for medical applications. The present study focuses on a strategy which resides in the encapsulation of AuNP in large polymeric NP to avoid the glomerular filtration and then to prolong the vascular residence time. An original encapsulation procedure using the polyethyleneimine (PEI) was set up to electrostatically entrap AuNP in biodegradable poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol -PLGA (PLGA-PEG) NP. Hydrodynamic diameters of NP were dependent of the PEI/Au ratio and comprised between 115 and 196 nm for ratios equal or superior to 4. Encapsulation yield was close to 90 % whereas no loading was observed without PEI. No toxicity was observed after 24 h exposure in hepatocyte cell-lines. Entrapement of AuNP in polymeric nanocarriers facilitated the passive uptake in cancer cells after only 2 h incubation. In healthy rat, the encapsulation allowed increasing the gold concentration in the blood within the first hour after intravenous administration. Polymeric nanoparticles were sequestered in the liver and the spleen rather than the kidneys. T-weighted magnetic resonance demonstrated that encapsulation process did not alter the contrast agent properties of gadolinium. The encapsulation of the gold nanoparticles in PLGA particles paves the way to innovative imaging-guided anticancer therapies in personalized medicine.
Mots clés
Gadolinium, Gold nanoparticles, MRI, PLGA nanoparticles, Theranostic
Référence
Colloids Surf B Biointerfaces. 2021 May 23;205:111875