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Effects of Hmga2 Sirna and Doxorubicin Dual Delivery by Chitosan Nanoparticles on Cytotoxicity and Gene Expression of Ht-29 Colorectal Cancer Cell Line Publisher Pubmed



Siahmansouri H1, 2, 3 ; Somi MH1 ; Babaloo Z3 ; Baradaran B3 ; Jadidiniaragh F4 ; Atyabi F5 ; Mohammadi H3 ; Ahmadi M3 ; Yousefi M3, 6
Authors
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Authors Affiliations
  1. 1. Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  2. 2. Student's Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  3. 3. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  4. 4. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Source: Journal of Pharmacy and Pharmacology Published:2016


Abstract

Objective: Over-expressions of HMGA2, vimentin and MMP-9 and downregulation of E-cadherin occur on colorectal cancer cells followed by a reduction in let-7 as a regulatory factor. In this study, we first used carboxymethyl dextran (CMD)–chitosan nanoparticles (ChNPs) platform to encapsulate HMGA2 siRNA and doxorubicin (DOX), and then, we evaluated the efficacy of the simultaneous delivery of siRNA/drug on viability and gene expression of HT-29 cell lines. Methods: ChNPs characteristics were determined by a dynamic light scattering and zeta sizer. Morphology of loaded ChNPs was assessed by scanning electron microscopy, and Fourier transform infrared spectroscopy was used to confirm the conjugation of ChNP/siRNA/DOX/CMD. Cell viability and relative mRNA expression were evaluated by MTT assay and real-time PCR, respectively. Key finding: The prepared ChNPs had high efficiency for siRNA and drug encapsulation (78% and 75%) and were stable against serum and heparin. ChNP/siRNA/DOX/CMD was more effective to induce tumour cell death and also could significantly reduce the expressions of HMGA2, vimentin as well as MMP-9 and increase E-cadherin expression. Conclusion: In conclusion, our results revealed that dual delivery of a key gene siRNA and appropriate anticancer drug have great impact on the treatment of colorectal cancer. © 2016 Royal Pharmaceutical Society
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