title: Thiolated carboxymethyl dextran as a nanocarrier for colon delivery of hSET1 antisense: In vitro stability and efficiency study.
abstract: Gene therapy is an optimistic approach in cancer treatment. However, for efficient delivery of gene materials, designing an appropriate vector is necessary. Polyelectrolyte complexes (PECs) of chitosan and dextran could be considered a proper nanoparticulate carrier for sensitive biomaterials. In this study, PECs of chitosan and thiolated dextran were used as either an injectable or oral gene delivery system. hSET1 antisense was loaded into the PECs to suppress proliferation of colon cancer cell line. The prepared nanoparticles have ~115nm diameter size and positive zeta potential with high mucoadhesion properties. They are able to protect antisense from degradation in serum and biorelevant fluids (FaSSIF and FaSSGF). Furthermore, prepared nanoparticles demonstrated superior cellular penetration and inhibitory effect on SW480 colon cancer cell proliferation. All nanoparticles significantly down regulated hSET1 in comparison with naked antisense. It can be concluded that thiolated PECs have potential use for injectable or oral delivery of nucleic acids such as antisense.
authors.affiliation: Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran. Electronic address: Melika.kiani@gmail.com.
authors.forename: Melika
authors.initials: M
authors.lastname: Kiani
authors.affiliation: Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran. Electronic address: mirzazadehf@yahoo.com.
authors.forename: Farnaz Sadat
authors.initials: FS
authors.lastname: Mirzazadeh Tekie
authors.affiliation: Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran. Electronic address: mdinarvand@hotmail.com.
authors.forename: Meshkat
authors.initials: M
authors.lastname: Dinarvand
authors.affiliation: Stem Cell Technology Research Centre, P.O. Box 14155-3174, Tehran, Iran; Department of Hematology, School of Medical Sciences, Tarbiat Modares University, P.O. Box: 14115-111, Tehran, Iran. Electronic address: soleim_m@modares.ac.ir.
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dinarvand@tums.ac.ir.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
authors.affiliation: Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: atyabifa@tums.ac.ir.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D003106:Colon / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry*; D015536:Down-Regulation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D016376:Oligonucleotides, Antisense / Q000378:metabolism*; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014162:Transfection
chemical_list: D003911:Dextrans; D004337:Drug Carriers; D016376:Oligonucleotides, Antisense; D013438:Sulfhydryl Compounds; D048271:Chitosan; C014392:carboxymethyl dextran; D011495:Histone-Lysine N-Methyltransferase; C526068:Setd1A protein, human
keywords: Chitosan; Colon cancer; Oral delivery; Thiolated dextran; hSET1 antisense