title: SiRNA/DOX lodeded chitosan based nanoparticles: Development, Characterization and in vitro evaluation on A549 lung cancer cell line.
abstract: High-mobility group AT-hook2 (HMGA2), involved in epithelial mesenchymal transition (EMT) process, has a pivotal role in lung cancer metastasis. Lung cancer therapy with HMGA2 suppressing small interfering RNA (siRNA) has been introduced recently while doxorubicin (DOX) has been used as a frequent cancer chemotherapy agent. Both reagents have been faced with obstacles in clinic which make them ineffective. NanoParticles (NPs) provided a platform for efficient co delivery of the anticancer drugs. The aim of this study was production and in vitro characterization of different pharmacological groups (siRNA, DOX or siRNA-DOX) of carboxymethyl dextran thrimethyl chitosan nanoparticles (CMDTMChiNPs) on cytotoxicity, gene expression, apoptosis and migration of metastatic lung cancer cell line (A-549). CMDTMChiNPs were synthesized and encapsulated with siRNA, DOX or siRNA-DOX. Then the effects of HMGA2 siRNA and DOX co delivery was assessed in A549 viability and target genes (HMGA2, Ecadherin, vimentin and MMP9) by MTT and real time PCR, respectively. In addition capability of apoptosis induction and anti-migratory features of formulated NPs were analyzed by flowcytometry and wound healing assays. SiRNA-DOX-CMDTM ChiNPs approximate size were 207±5 with poly dispersity index (PDI) and zeta potential of 0.4 and 16.3±0.3, respectively. NPs loaded with DOX and siRNA were the most efficient drug formulations in A549 cell cytotoxicity, altering of EMT markers, apoptosis induction and migration inhibition. Generally our results showed that co delivery of HMGA2 siRNA and DOX by novel designed CMDTMChiNPs is a new therapeutic approach with great potential efficiency for lung cancer treatment.
authors.affiliation: Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences Tabriz Iran.
authors.forename: M
authors.initials: M
authors.lastname: Seifi-Najmi
authors.affiliation: Tabriz University of Medical Sciences Immunology research center Tabriz Iran.
authors.forename: M
authors.initials: M
authors.lastname: Hajivalili
authors.affiliation: University of Tabriz Department of Animal Biology, Faculty of Natural Sciences Tabriz Iran.
authors.forename: R
authors.initials: R
authors.lastname: Safaralizadeh
authors.affiliation: Tabriz University of Medical Sciences Immunology research center Tabriz Iran.
authors.forename: S
authors.initials: S
authors.lastname: Sadreddini
authors.affiliation: Tarbiat Modares University Department of Hematology and Blood banking Tehran Iran.
authors.forename: S
authors.initials: S
authors.lastname: Esmaeili
authors.affiliation: University of Tabriz Department of Animal Biology, Faculty of Natural Sciences Tabriz Iran.
authors.forename: R
authors.initials: R
authors.lastname: Razavi
authors.affiliation: Tabriz University of Medical Sciences Immunology research center Tabriz Iran.
authors.forename: M
authors.initials: M
authors.lastname: Ahmadi
authors.affiliation: Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences Tabriz Iran.
authors.forename: H
authors.initials: H
authors.lastname: Mikaeili
authors.affiliation: Tabriz University of Medical Sciences Immunology research center Tabriz Iran.
authors.forename: B
authors.initials: B
authors.lastname: Baradaran
authors.affiliation: High Institute for Research and Education in Transfusion Medicine Blood Transfusion Research Center Tabriz Iran.
authors.forename: K
authors.initials: K
authors.lastname: Shams-Asenjan
authors.affiliation: Tabriz University of Medical Sciences Immunology research center Tabriz Iran Yousefime@tbzmed.ac.ir.
authors.forename: M
authors.initials: M
authors.lastname: Yousefi
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry* / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D025743:HMGA2 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017550:Spectroscopy, Fourier Transform Infrared; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D004337:Drug Carriers; D025743:HMGA2 Protein; D034741:RNA, Small Interfering; D014746:Vimentin; C514968:carboxymethyl-chitosan; D004317:Doxorubicin; D048271:Chitosan