title: Enhanced cellular uptake of folic acid-conjugated PLGA-PEG nanoparticles loaded with vincristine sulfate in human breast cancer.
abstract: The aim of this paper is to evaluate the cellular uptake of vincristine sulfate-loaded poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles with the folic acid modification (PLGA-PEG-folate NPs). PLGA-PEG-folate NPs were prepared using a water-oil-water emulsion solvent evaporation method. The particle size, surface morphology, drug encapsulation efficiency, and the drug release behavior were investigated. The NPs exhibited a biphasic drug release with a moderate initial burst followed by a sustained release profile. Internalization of the NPs labeled with coumarin- 6 by MCF-7 (Michigan Cancer Foundation-7) human breast cancer cells was quantitatively measured by microplate reader, and qualitatively analyzed by fluorescent microscopy and confocal laser scanning microscopy. The results showed PLGA-PEG-folate NPs achieved significantly higher cellular uptake in the folic acid receptor overexpressed MCF-7 cells, compared to PLGA-mPEG NPs without the folic acid modification. Due to the enhanced cellular uptake, PLGA-PEG-folate NPs displayed the highest cytotoxicity. Judged by IC(50) after 24 h culture, the therapeutic effects of the drug formulated in the NPs with surface modification could be 1.52 times, 3.91 times higher than that of PLGA-mPEG NPs and free vincristine sulfate, respectively.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jianian
authors.initials: J
authors.lastname: Chen
authors.forename: Shaoshun
authors.initials: S
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.forename: Huijuan
authors.initials: H
authors.lastname: He
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002470:Cell Survival; D004337:Drug Carriers / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D014750:Vincristine; D005492:Folic Acid