ABSTRACT
miR-145 is a tumor suppressive miRNA which is abnormally reduced in different cancers. miR-145 overexpression reduces cancer migration, invasion, and cell adhesion. Increasing miR-145 level using suitable and efficient gene delivery systems could be valuable in cancer treatment. In this study, a redox-responsive miR-145 conjugated thiolated dextran (TD-miR) was prepared. Also, polyelectrolyte complexes (PECs) of TD-miR and chitosan were fabricated and decorated with anti nucleolin aptamer, AS1411 (apt-PEC). The size of the PECs was between 40-270 nm, and the zeta potential was varied according to the TD-miR to chitosan molar ratio. The outcomes of cellular studies indicated the excellence of the apt-PEC as a duel targeted delivery system and the PECs composed of chitosan 18 kDa with TD-miR to chitosan ratio of 5. TD-miR and the PECs are appropriate as the smart gene delivery systems which preserve and transfect the cargo and release it in cytoplasm.
Subject(s)
Aptamers, Nucleotide , Chitosan , Dextrans , Drug Delivery Systems , Glutathione/metabolism , MicroRNAs , Nanoparticles , Neoplasms/drug therapy , Aptamers, Nucleotide/chemistry , Aptamers, Nucleotide/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Dextrans/chemistry , Dextrans/pharmacology , Humans , MCF-7 Cells , MicroRNAs/chemistry , MicroRNAs/pharmacology , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Neoplasms/metabolismABSTRACT
Chitosan (Ch) nanoparticles have emerged as a promising vector for gene delivery, nonetheless slow dissociation rate of the nanoparticles in cytoplasm is a drawback of using Ch. Herein, the Ch-mediated gene delivery was improved using PECs of Ch and carboxymethyl dextran (CMD) to transfer the micro RNA-145 (miR-145). The optimized nano PEC preparation method and effects of Ch molecular weight (Mw) and a CMD to Ch molar ratio (CMD:Ch) on physical characteristics and in vitro efficacy of the nano PECs was determined. The size of the nano PECs depended on the preparation method, Ch Mw, and CMD:Ch ratio. Also, the Ch Mw and CMD:Ch affected stability of the miR-145 PECs in presence of heparin. In vitro tests indicated the different gene transfection efficiency of the nano PECs with various compositions. As a novel vector, these nano PECs have excellent promise for gene delivery with an adequate balance between a complex stability and dissociation rate.
