title: Folate-modified lipid-polymer hybrid nanoparticles for targeted paclitaxel delivery.
abstract: The purpose of this study was to develop a novel lipid-polymer hybrid drug carrier comprised of folate (FA) modified lipid-shell and polymer-core nanoparticles (FLPNPs) for sustained, controlled, and targeted delivery of paclitaxel (PTX). The core-shell NPs consist of 1) a poly(ε-caprolactone) hydrophobic core based on self-assembly of poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) amphiphilic copolymers, 2) a lipid monolayer formed with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (DSPE-PEG2000), 3) a targeting ligand (FA) on the surface, and were prepared using a thin-film hydration and ultrasonic dispersion method. Transmission electron microscopy and dynamic light scattering analysis confirmed the coating of the lipid monolayer on the hydrophobic polymer core. Physicochemical characterizations of PTX-loaded FLPNPs, such as particle size and size distribution, zeta potential, morphology, drug loading content, encapsulation efficiency, and in vitro drug release, were also evaluated. Fluorescent microscopy proved the internalization efficiency and targeting ability of the folate conjugated on the lipid monolayer for the EMT6 cancer cells which overexpress folate receptor. In vitro cytotoxicity assay demonstrated that the cytotoxic effect of PTX-loaded FLPNPs was lower than that of Taxol(®), but higher than that of PTX-loaded LPNPs (without folate conjugation). In EMT6 breast tumor model, intratumoral administration of PTX-loaded FLPNPs showed similar antitumor efficacy but low toxicity compared to Taxol(®). More importantly, PTX-loaded FLPNPs showed greater tumor growth inhibition (65.78%) than the nontargeted PTX-loaded LPNPs (48.38%) (P<0.05). These findings indicated that the PTX loaded-FLPNPs with mixed lipid monolayer shell and biodegradable polymer core would be a promising nanosized drug formulation for tumor-targeted therapy.
authors.affiliation: Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, People's Republic of China.
authors.forename: Linhua
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, People's Republic of China.
authors.forename: Dunwan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Dong
authors.affiliation: Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, People's Republic of China.
authors.forename: Hongfan
authors.initials: H
authors.lastname: Sun
authors.affiliation: Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, People's Republic of China.
authors.forename: Cunxian
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, People's Republic of China.
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D005260:Female; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry; D008807:Mice, Inbred BALB C; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage*; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D004337:Drug Carriers; D008055:Lipids; D008823:Micelles; D010714:Phosphatidylethanolamines; D011091:Polyesters; D011108:Polymers; C515340:poly(epsilon-caprolactone)-b-poly(ethyleneglycol)-b-poly(epsilon-caprolactone); D011092:Polyethylene Glycols; D005492:Folic Acid; D017239:Paclitaxel
keywords: PCL-PEG-PCL; drug delivery; folate; lipid–polymer hybrid nanoparticles; paclitaxel
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