Cyclodextrin-assisted assembly of PEGylated polyester nanoparticles decorated with folate

In the last decades, nano-oncologicals bearing a polyethylene glycol (PEG) coating are being emerging as biomimetic devices able to drive their drug cargo to solid tumors through passive mechanisms. To improve selectivity toward cancer cells, nanocarriers decorated with the small ligand folate have been widely investigated. Nevertheless, a great challenge remains the effective exposition of folate on nanoparticles (NPs), which is a key prerequisite to ensure the correct binding to receptor and the following endocytic uptake. On these premises, in this study we propose a novel strategy to produce core-shell folate-targeted NPs based on diblock copolymers of poly(epsilon-caprolactone) (PCL) and PEG through the aid of (2-hydroxypropyl)-beta-cyclodextrin (HPPCD). PCL4300-PEG(2000) and PCL4300-PEG(2000)-Fol copolymers were synthesized, characterized and employed to produce NPs without and with HP beta CD by a melting/sonication procedure. Colloidal properties of targeted NPs produced with HP beta CD demonstrated a highly extended conformation of PEG chains in the shell, an enhanced interaction with a specific antibody against folate and a higher uptake in cells overexpressing folate receptor. Overall, these results suggest that proper manipulation of PEG shell conformation through HP beta CD can represent a novel non-covalent strategy to modify shell features. (C) 2016 Elsevier B.V. All rights reserved.