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.
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http://dx.doi.org/10.1016/j.msec.2016.02.009 | DOI Listing |
Mater Sci Eng C Mater Biol Appl
May 2016
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:
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.
View Article and Find Full Text PDFInt J Biol Macromol
February 2016
Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1714614411, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:
An oral delivery system intended for treatment of colon cancer in HT29 cancerous cells was investigated by encapsulating hSET1 antisense and SN38 anticancer in nanoparticles based on cysteine trimethyl chitosan (cysTMC) and carboxymethyl dextran (CMD). Studies have shown hSET1 as the main type of histone methyltransferase (HMT) complex, is significantly overexpressed in malignant cells. In this study, hSET1 antisense was employed to inhibit gene expression.
View Article and Find Full Text PDFBiochem Pharmacol
May 2009
Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Histone-methyl transferases (HMTs) are key enzymes that post-translationally modify histones, and serve key role in gene expression, epigenetic regulation, and as determinants of survival in malignant cells. Recent studies have shed light on the role of hSET1 which is a key element of highly conserved multi-protein HMT complex that catalyze methylation of histone H3 lysine 4 (H3K4) regulating expression of specific proteins important for the malignant phenotype. To understand the importance of differential expression of H3K4 HMTs in cancer, we specifically down-regulated hSET1 the only H3K4 specific histone-methyl transferase present in yeast as well as in human that is directly involved in gene expression.
View Article and Find Full Text PDFBiochim Biophys Acta
January 2008
Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas 76019, USA.
Human encodes several histone H3-Lysine 4 (H3K4) specific methyl-transferases (HMTs) such as MLL1 (mixed lineage leukemia 1), MLL2, MLL3, hSet1 etc, that play critical roles in gene expression. These HMTs are present as distinct multi-protein complexes with several proteins in common. Herein, we have affinity purified and characterized human CpG binding protein (CGBP) and its interacting proteins from human cells.
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