title: Cyclodextrin-assisted assembly of PEGylated polyester nanoparticles decorated with folate.
abstract: 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(ε-caprolactone) (PCL) and PEG through the aid of (2-hydroxypropyl)-β-cyclodextrin (HPβCD). PCL4300-PEG2000 and PCL4300-PEG2000-Fol copolymers were synthesized, characterized and employed to produce NPs without and with HPβCD by a melting/sonication procedure. Colloidal properties of targeted NPs produced with HPβCD 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 HPβCD can represent a novel non-covalent strategy to modify shell features.
authors: Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors: Claudia
authors: C
authors: Conte
authors: Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors: Iolanda
authors: I
authors: Fotticchia
authors: Department of Chemical Sciences, University of Napoli Federico II, Via Cintia, 80126 Napoli, Italy.
authors: Pasquale
authors: P
authors: Tirino
authors: Department of Biology, University of Padova, via U. Bassi 58/b, 35121 Padova, Italy.
authors: Francesca
authors: F
authors: Moret
authors: Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors: Bruno
authors: B
authors: Pagano
authors: Institute of Molecular Sciences, CNRS, Université Paris-Sud, Université Paris Saclay, 91400 Orsay, France.
authors: Ruxandra
authors: R
authors: Gref
authors: Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors: Francesca
authors: F
authors: Ungaro
authors: Department of Biology, University of Padova, via U. Bassi 58/b, 35121 Padova, Italy.
authors: Elena
authors: E
authors: Reddi
authors: Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors: Concetta
authors: C
authors: Giancola
authors: Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy. Electronic address: quaglia@unina.it.
authors: Fabiana
authors: F
authors: Quaglia
mesh_terms: D000072283:A549 Cells; D002151:Calorimetry / Q000379:methods; D002208:Caproates / Q000737:chemistry; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D004705:Endocytosis; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007783:Lactones / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D002208:Caproates; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D007783:Lactones; D011091:Polyesters; D047392:beta-Cyclodextrins; D011092:Polyethylene Glycols; C121056:caprolactone; D005492:Folic Acid
keywords: Biodegradable polymers; Folate; Nanoparticles; Pegylation; Poly(ε-caprolactone)