title: Aptamer-functionalized PEG-PLGA nanoparticles for enhanced anti-glioma drug delivery.
abstract: Targeted delivery of therapeutic nanoparticles in a disease-specific manner represents a potentially powerful technology especially when treating infiltrative brain tumors such as gliomas. We developed a nanoparticulate drug delivery system decorated with AS1411 (Ap), a DNA aptamer specifically binding to nucleolin which was highly expressed in the plasma membrane of both cancer cells and endothelial cells in angiogenic blood vessels, as the targeting ligand to facilitate anti-glioma delivery of paclitaxel (PTX). Ap was conjugated to the surface of PEG-PLGA nanoparticles (NP) via an EDC/NHS technique. With the conjugation confirmed by Urea PAGE and XPS, the resulting Ap-PTX-NP was uniformly round with particle size at 156.0 ± 54.8 nm and zeta potential at -32.93 ± 3.1 mV. Ap-nucleolin interaction significantly enhanced cellular association of nanoparticles in C6 glioma cells, and increased the cytotoxicity of its payload. Prolonged circulation and enhanced PTX accumulation at the tumor site was achieved for Ap-PTX-NP, which eventually obtained significantly higher tumor inhibition on mice bearing C6 glioma xenografts and prolonged animal survival on rats bearing intracranial C6 gliomas when compared with PTX-NP and Taxol(®). The results of this contribution demonstrated the potential utility of AS1411-functionalized nanoparticles for a therapeutic application in the treatment of gliomas.
authors.affiliation: Department of Pharmaceutics, Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai 201203, PR China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Guo
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gao
authors.forename: Lina
authors.initials: L
authors.lastname: Su
authors.forename: Huimin
authors.initials: H
authors.lastname: Xia
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Gu
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
authors.forename: Lei
authors.initials: L
authors.lastname: Yao
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Hongzhuan
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D004591:Electrophoresis, Polyacrylamide Gel; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D020128:Inhibitory Concentration 50; D007275:Injections, Intravenous; D053208:Kaplan-Meier Estimate; D019344:Lactic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010316:Particle Size; D056951:Photoelectron Spectroscopy; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D055672:Static Electricity; D013499:Surface Properties / Q000187:drug effects; D014018:Tissue Distribution / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: C513936:AGRO 100; D052157:Aptamers, Nucleotide; D009838:Oligodeoxyribonucleotides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D017239:Paclitaxel