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Oral Delivery of Nanoparticles Containing Anticancer Sn38 and Hset1 Antisense for Dual Therapy of Colon Cancer Publisher Pubmed



Dinarvand M1 ; Kiani M1 ; Mirzazadeh F1 ; Esmaeili A1 ; Mirzaie Z2 ; Soleimani M3 ; Dinarvand R1, 2 ; Atyabi F1, 2
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1714614411, Iran
  2. 2. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Source: International Journal of Biological Macromolecules Published:2015


Abstract

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. Additionally, SN38 was incorporated into nanoparticles to enhance the efficiency of the system by inhibition of topoisomerase 1. CysTMC was synthetized and characterized by 1H NMR and FTIR. Nanoparticles were prepared through complexation of CMD and cysTMC. Particle size and surface charge was 100-150nm and 17-21mV respectively with drug content of around 2.6%. Gel electrophoresis assay proved the stability of antisense in simulated gastric and intestinal fluids. Nanoparticles showed high mucoadhesion and glutathione responsive release. Cellular uptake was observed by confocal microscopy and quantified by flow cytometry. Cytotoxicity of NPs was assessed using MTT assay. Results showed hSET1/SN38 nanoparticles had significantly higher cytotoxicity against HT29 cells compared with nanoparticles containing SN38, free SN38 or naked hSET1. Therefore, present system could be considered an effective combination therapy of highly hydrophobic SN38 and hSET1. © 2015 Elsevier B.V.