Hepatocyte-targeted fluorescent nanoparticles based on a polyaspartamide for potential theranostic applications. (23rd July 2015)

• Record Type: Journal Article
• Authors: Craparo, Emanuela Fabiola; Licciardi, Mariano; Conigliaro, Alice; Palumbo, Fabio Salvatore; Giammona, Gaetano; Alessandro, Riccardo; De Leo, Giacomo; Cavallaro, Gennara
• Is Part Of: Polymer. Volume 70(2015)
• Page Start: 257
• Page End: 270
• Publication Date: 2015-07-23
• Subjects: Active targeting -- α, β-Poly-(N-2-hydroxyethyl)-dl-aspartamide (PHEA) -- Fluorescence imaging -- Graft copolymers -- Nanoparticles; Polymers -- Periodicals; Polymerization -- Periodicals; Polymères -- Périodiques; Polymérisation -- Périodiques; 547.7
• DOI: 10.1016/j.polymer.2015.06.009
• Languages: English
• ISSNs: 0032-3861

Abstract

Abstract: Here, the synthesis of a galactosylated amphiphilic copolymer bearing rhodamine (RhB) moieties and its use for the preparation of polymeric fluorescent nanoparticles for potential applications in therapy and diagnosis are described. To do this, firstly, a fluorescent derivative of α, β-poly( N -2-hydroxyethyl)-d, l -aspartamide (PHEA) was synthesized by chemical reaction with RhB, and with polylactic acid (PLA), to obtain PHEA-RhB-PLA. Then, the derivatization of PHEA-RhB-PLA with GAL-PEG-NH2 allows obtaining PHEA-RhB-PLA-PEG-GAL copolymer, with derivatization degrees in -PLA and -PEG-GAL equal to 1.9 mol% and 4.5 mol%, respectively. Starting from this copolymer, liver-targeted fluorescent nanoparticles were prepared by high pressure homogenization–solvent evaporation method, and showed nanoscaled size, slightly negative zeta potential and spherical shape. Chemical and enzymatic stability of fluorescent dye covalently linked to the copolymer backbone by ester linkage was demonstrated until 4 days of incubation. Finally, thanks to the covalently-linked fluorescent RhB, it was demonstrated that these galactosylated nanoparticles interact with HepG2 cells that are positive for the asialoglycoprotein receptor (ASGPR), while these do not interact with HeLa cells that are negative for the same receptor, demonstrating the contributor of ASGPR to the internalization process. Graphical abstract: Highlights: Liver-targeted fluorescent nanoparticles for potential in vitro and in vivo imaging were realised. These nanoparticles have nanoscaled size, slightly negative zeta potential and spherical shape. Chemical and enzymatic stability of the ester linkage between RhB and copolymer was demonstrated until 4 days. Fluorescent nanoparticles (FNPs) bearing GAL moieties are endocytosed by HepG2 cells, while not by HeLa cells. The contributor of ASGPR to the internalization process was demonstrated.