NIR-emissive PEG-b-TCL micelles for breast tumor imaging and minimally invasive pharmacokinetic analysis.
Fiche publication
Date publication
septembre 2017
Journal
Nanoscale
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DETAPPE Alexandre
Tous les auteurs :
Hofmann CL, O'Sullivan MC, Detappe A, Yu Y, Yang X, Qi W, Landon CD, Therien MJ, Dewhirst MW, Ghoroghchian PP, Palmer GM
Lien Pubmed
Résumé
Motivated by the goal of developing a fully biodegradable optical contrast agent with translational clinical potential, a nanoparticle delivery vehicle was generated from the self-assembly of poly(ethylene-glycol)-block-poly(trimethylene carbonate-co-caprolactone) (PEG-b-TCL) copolymers. Cryogenic transmission electron microscopy verified that PEG-b-TCL-based micelles were formed at low solution temperatures (∼38 °C). Detailed spectroscopic experiments validated facile loading of large quantities of the high emission dipole strength, tris(porphyrin)-based fluorophore PZn within their cores, and the micelles displayed negligible in vitro and in vivo toxicities in model systems. The pharmacokinetics and biodistribution of PZn-loaded PEG-b-TCL-based micelles injected intravenously were determined via ex vivo near-infrared (NIR) imaging of PZn emission in microcapillary tubes containing minute quantities of blood, to establish a novel method for minimally invasive pharmacokinetic monitoring. The in vivo circulatory half-life of the PEG-b-TCL-based micelles was found to be ∼19.6 h. Additionally, longitudinal in vivo imaging of orthotopically transplanted breast tumors enabled determination of micelle biodistribution that correlated to ex vivo imaging results, demonstrating accumulation predominantly within the tumors and livers of mice. The PEG-b-TCL-based micelles quickly extravasated within 4T1 orthotopic mammary carcinomas, exhibiting peak accumulation at ∼48 h following intravenous tail-vein injection. In summary, PEG-b-TCL-based micelles demonstrated favorable characteristics for further development as in vivo optical contrast agents for minimally invasive imaging of breast tumors.
Mots clés
Animals, Breast Neoplasms, diagnostic imaging, Contrast Media, Female, Human Umbilical Vein Endothelial Cells, Humans, Infrared Rays, Mice, Mice, Inbred BALB C, Micelles, Polyesters, Polyethylene Glycols, Tissue Distribution
Référence
Nanoscale. 2017 Sep 21;9(36):13465-13476