title: Study and evaluation of nucleolin-targeted delivery of magnetic PLGA-PEG nanospheres loaded with doxorubicin to C6 glioma cells compared with low nucleolin-expressing L929 cells.
abstract: Magnetic nanoparticulate systems based on polymeric materials such as poly (lactic-co-glycolic acid) (PLGA1) are being studied for their potential applications in targeted therapy and imaging of malignant tumors. In the current study, superparamagnetic iron oxide nanocrystals (SPIONs2) and doxorubicin (Dox3) were entrapped in the PLGA-based nanoparticles via a modified multiple emulsion solvent evaporation method. Furthermore, SPIO/Dox-NPs4were conjugated to anti-nucleolin AS1411 aptamer (Apt5) and their targeting ability was investigated in high nucleolin-expressing C6 glioma cells compared to low nucleolin-expressing L929 cells. The NPs exhibited a narrow size distribution with mean diameter of ~170nm and an appropriate SPION content (~18% of total polymer weight) with a sufficient saturation magnetization value of 5.9emu/g which is suitable for imaging objectives. They manifested an increased Dox release at pH5.5 compared to pH7.4, with initial burst release (within 24h) followed by sustained release of Dox for 36days. The Apt conjugation to NPs enhanced cellular uptake of Dox in C6 glioma cells compared to L929 cells. Similarly, the Apt-NPs increased the cytotoxicity effect of Dox compared with NPs and Dox solution (f-Dox) alone. In conclusion, the Apt-NPs were found to be a promising delivery system for therapeutic and diagnostic purposes.
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Jafar
authors.initials: J
authors.lastname: Mosafer
authors.affiliation: School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran.
authors.forename: Manouchehr
authors.initials: M
authors.lastname: Teymouri
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Tafaghodi
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Ramezanim@mums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000737:chemistry / Q000633:toxicity; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry; D004317:Doxorubicin / Q000097:blood / Q000737:chemistry* / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006207:Half-Life; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000737:chemistry*; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D054118:Nanospheres / Q000737:chemistry*; D010316:Particle Size; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D000097796:Nucleolin
chemical_list: D000903:Antibiotics, Antineoplastic; D052157:Aptamers, Nucleotide; D003911:Dextrans; D004317:Doxorubicin; D004337:Drug Carriers; D019344:Lactic Acid; D058185:Magnetite Nanoparticles; D010750:Phosphoproteins; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C065507:ferumoxides
keywords: Aptamer; Doxorubicin; Glioma cell; Nucleolin; PLGA; SPION