title: AS1411 Aptamer-Decorated Biodegradable Polyethylene Glycol-Poly(lactic-co-glycolic acid) Nanopolymersomes for the Targeted Delivery of Gemcitabine to Non-Small Cell Lung Cancer In Vitro.
abstract: Molecularly targeted drug delivery systems represent a novel therapeutic strategy in the treatment of different cancers. In the present study, we have developed gemcitabine (GEM)-loaded AS1411 aptamer surface-decorated polyethylene glycol-poly(lactic-co-glycolic acid) nanopolymersome (Apt-GEM-NP) to target nucleolin-overexpressing non-small cell lung cancer (NSCLC; A549). The prepared Apt-GEM-NP showed average particle size of 128 ± 5.23 nm and spherical morphology with encapsulation efficiency and loading content of 95.32 ± 2.37% and 8.61 ± 0.27%, respectively. Apt-GEM-NP exhibited a controlled release pattern. A sustained release of drug in physiological conditions will greatly improve the chemotherapeutic efficiency of a system. Enhanced cellular uptake and the cytotoxicity of aptamer-conjugated nanoparticles (NPs) in A549 cancer cells obviously verified nucleolin-mediated receptor-based active targeting. Nucleolin-mediated internalization of the targeted polymeric NP was further confirmed by flow cytometry and fluorescence microscopy. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay clearly showed the enhanced cell proliferation inhibitory effect of AS1411-conjugated NP on account of the selective delivery of GEM to the nucleolin-overexpressing cancer cells. Our results showed that AS1411 aptamer conjugation on the surface of NP could be a potential treatment strategy for A549 as a nucleolin-overexpressing cell line. This suggests that AS1411-GEM-NPs could be potentially used for the treatment of NSCLC.
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mona
authors.initials: M
authors.lastname: Alibolandi
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: abnouskh@mums.ac.ir.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: hadizadehf@mums.ac.ir.
authors.forename: Farzin
authors.initials: F
authors.lastname: Hadizadeh
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000378:metabolism*; D052157:Aptamers, Nucleotide; D016466:CHO Cells; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000378:metabolism*; D011091:Polyesters; D011092:Polyethylene Glycols; D011108:Polymers / Q000008:administration & dosage / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: C513936:AGRO 100; D000964:Antimetabolites, Antineoplastic; D052157:Aptamers, Nucleotide; D009838:Oligodeoxyribonucleotides; D011091:Polyesters; D011108:Polymers; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D003841:Deoxycytidine; D011092:Polyethylene Glycols; D000093542:Gemcitabine
keywords: PLGA; cancer chemotherapy; drug delivery system; encapsulation; nanoparticle; polymeric drug delivery systems; targeted drug delivery