title: Protein corona hampers targeting potential of MUC1 aptamer functionalized SN-38 core-shell nanoparticles.
abstract: Nanoparticles have been considered to improve delivery and physicochemical characteristics of bioactive agents in recent years. In this study, a core-shell chitosan nanoparticulate system was prepared for the targeted delivery of SN-38. SN-38, an active metabolite of camptothecin, conjugated to hyaluronic acid (HA) was used as the shell of chitosan nanoparticles decorated with MUC1 aptamer. The conjugation was confirmed by UV and (1)H NMR techniques. Targeting efficiency was evaluated by confocal microscopy and flow cytometry. It was shown that MUC1 decoration increased the uptake of nanoparticles by HT29 cells, MUC1 positive cell line, while CHO as MUC1 negative cell line showed no enhanced uptake of decorated nanoparticles. Compared to non-targeted nanoparticles, flow cytometric annexin V/PI analyses showed that the nanoparticles exert cytotoxicity through apoptosis. It was, however, shown that protein corona adsorption at the surface of nanoparticles hampered the cytotoxicity of nanoparticles, as there was no difference between the cytotoxicity of targeted and non-targeted nanoparticles, when treated with bovine serum albumin prior to cytotoxicity study.
authors: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Behrang Shiri
authors: BS
authors: Varnamkhasti
authors: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors: Hosniyeh
authors: H
authors: Hosseinzadeh
authors: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Morteza
authors: M
authors: Azhdarzadeh
authors: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Seyed Yaser
authors: SY
authors: Vafaei
authors: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Mehdi
authors: M
authors: Esfandyari-Manesh
authors: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Zahra H
authors: ZH
authors: Mirzaie
authors: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mohsen
authors: M
authors: Amini
authors: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors: Seyed Nasser
authors: SN
authors: Ostad
authors: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors: Fatemeh
authors: F
authors: Atyabi
authors: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dinarvand@tums.ac.ir.
authors: Rassoul
authors: R
authors: Dinarvand
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D052157:Aptamers, Nucleotide; D002152:Calorimetry, Differential Scanning; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D006224:Cricetinae; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D000077146:Irinotecan; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D018396:Mucin-1 / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D000066970:Protein Corona / Q000378:metabolism*
chemical_list: D052157:Aptamers, Nucleotide; D004337:Drug Carriers; C455419:MUC-X protein, human; D018396:Mucin-1; D000066970:Protein Corona; D000077146:Irinotecan; D006820:Hyaluronic Acid; D048271:Chitosan; D002166:Camptothecin
keywords: Hyaluronic acid; MUC1 aptamer; Nanoparticle; Protein corona; SN-38