title: Folate-decorated hybrid polymeric nanoparticles for chemically and physically combined paclitaxel loading and targeted delivery.
abstract: In this study, folate-functionalized hybrid polymeric nanoparticles (NPs) were prepared as carriers of low water solubility paclitaxel for tumor targeting, which were composed of monomethoxy-poly(ethylene glycol)-b-poly(lactide)-paclitaxel (MPEG-PLA-paclitaxel) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-folate (TPGS-FOL). NPs with various weight ratios of MPEG-PLA-paclitaxel and TPGS-FOL were prepared using a solvent extraction/evaporation method, which can also physically encapsulate paclitaxel. The size, size distribution, surface charge, and morphology of the drug-loaded NPs were characterized using a Zetasizer Nano ZS, scanning electron microscope (SEM), and atomic force microscopy (AFM). The encapsulation and drug loading efficiencies of these polymeric NPs are analyzed using high-performance liquid chromatography (HPLC) at 227 nm. The combination of covalent coupling and physical encapsulation is found to improve the loading of paclitaxel in NPs greatly. The in vitro antitumor activity of the drug-loaded NPs is assessed using a standard method of transcriptional and translational (MTT) assays against HeLa and glioma C6 cells. When the cells were exposed to NPs with the same paclitaxel weights, cell viability decreases in relation to the increase in TPGS-FOL in drug-loaded NPs. To investigate drug-loaded NP cellular uptake, the fluorescent dye coumarin-6 is utilized as a model drug and enveloped in NPs with 0 or 50% TPGS-FOL. Confocal laser scanning microscopy (CLSM) analysis shows that cellular uptake is lower for coumarin-6-loaded NPs with 0% TPGS-FOL than those with 50% TPGS-FOL. However, no difference for NIH 3T3 cells with normally expressed folate receptors is found. Results from in vitro antitumor activity and cellular uptake assay demonstrate that folic acid promotes drug-loaded NP cellular uptake through folate receptor-mediated endocytosis (RME). All of these results demonstrate that folate-decorated hybrid polymeric NPs are potential carriers for tumor-targeted drug delivery.
authors.affiliation: Colleges of Science and Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wang
authors.forename: Wenming
authors.initials: W
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: Tu
authors.forename: Jianchun
authors.initials: J
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Song
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Nan
authors.initials: N
authors.lastname: Nie
authors.forename: Jinyi
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005492:Folic Acid / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011091:Polyesters; C492425:methoxy poly(ethylene glycol)-poly(lactide); D014810:Vitamin E; D011092:Polyethylene Glycols; D005492:Folic Acid; C014225:tocophersolan; D017239:Paclitaxel