Glutathione responsive chitosan-thiolated dextran conjugated miR-145 nanoparticles targeted with AS1411 aptamer for cancer treatment. (1st December 2018)

• Record Type: Journal Article
• Authors: Tekie, Farnaz Sadat Mirzazadeh; Soleimani, Masoud; Zakerian, Amir; Dinarvand, Meshkat; Amini, Mohsen; Dinarvand, Rassoul; Arefian, Ehsan; Atyabi, Fatemeh
• Is Part Of: Carbohydrate polymers. Volume 201(2018)
• Page Start: 131
• Page End: 140
• Publication Date: 2018-12-01
• Subjects: miRNAs micro RNAs -- PU-PEI polyurethane-short branch-polyethylenimine -- PEI polyethylenimine -- siRNA small interfering RNA -- TD thiolated dextran -- L-Cys L-cysteine -- CMD carboxymethyl dextran -- GSH glutathione -- PEC polyelectrolyte complexes -- Mw molecular weight -- TD-miR conjugate of TD and miR-145 -- EDTA ethylenediaminetetraacetic acid -- DTNB 5, 5-Dithiobis(2-nitrobenzoic acid) -- BSA bovine serum albumin -- FBS heat inactivated fetal bovine serum -- DMEM Dulbecco's modified Eagle's medium -- RT-PCR reverse transcription polymerase chain reaction -- MUC1 anti mucin1 -- FTIR Fourier transform infrared -- DTT dithiothreitol -- Ch9 chitosan 9 kDa -- Ch18 chitosan 18 kDa -- Rpm round per minute -- D/Ch dextran to chitosan molar ratio -- Cy5PECs Cy5 labeled PECs -- Apt-PEC AS1411 aptamer modified PEC -- DLS dynamic light scattering -- TEM transmission electron microscopy -- PDI polydispersity index -- SD standard deviation -- ANOVA one-way analysis of variance -- PBS phosphate buffer solution -- EDC 1-ethyl-3-(3-dimethylaminopropyl) carbadiimide -- NHS N-hydroxysuccinimide; miR-145 -- Thiolated dextran -- Chitosan -- PEC -- AS1411; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2018.08.060
• Languages: English
• ISSNs: 0144-8617

Abstract

Graphical abstract: Highlights: TD-miR redox responsive conjugates and PECs ensure miRNA stability against nucleases. Nano PECs were easily obtained by electrostatic complexation of TD-miR and chitosan. TD-miR and PECs could transfer anti-tumor miR-145 and suppress cell proliferation. PEC(18, 5) and targeted nano PECs with AS1411 are the most appropriate formulation. apt-PECs as dual targeted nanoparticles are useful for both chemo/bio-drug delivery. 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.