title: Effects of HMGA2 siRNA and doxorubicin dual delivery by chitosan nanoparticles on cytotoxicity and gene expression of HT-29 colorectal cancer cell line.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Student's Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.|Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Homayoon
authors.initials: H
authors.lastname: Siahmansouri
authors.affiliation: Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Somi
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Babaloo
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Baradaran
authors.affiliation: Department of Immunology , School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Jadidi-Niaragh
authors.affiliation: Department of Pharmaceutical Nanotechnology , Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Mohammadi
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Ahmadi
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Yousefi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015820:Cadherins / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D048271:Chitosan; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers; D004338:Drug Combinations; D016503:Drug Delivery Systems; D004355:Drug Stability; D025743:HMGA2 Protein / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053758:Nanoparticles; D010316:Particle Size; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D014746:Vimentin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D004337:Drug Carriers; D004338:Drug Combinations; D025743:HMGA2 Protein; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014746:Vimentin; D004317:Doxorubicin; D048271:Chitosan; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: HMGA2; colorectal cancer; doxorubicin; nanoparticle; siRNA