Homayoon Siahmansouri1,2,3, Mohammad Hossein Somi1, Zohreh Babaloo3, Behzad Baradaran3, Farhad Jadidi-Niaragh4, Fatemeh Atyabi5, Hamed Mohammadi3, Majid Ahmadi3, Mehdi Yousefi3,6. 1. Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Student's Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 4. Department of Immunology , School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. 5. Department of Pharmaceutical Nanotechnology , Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 6. Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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.
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.
Authors: Surendar Aravindhan; Sura Salman Ejam; Methaq Hadi Lafta; Alexander Markov; Alexei Valerievich Yumashev; Majid Ahmadi Journal: Cancer Cell Int Date: 2021-03-08 Impact factor: 5.722