EVALUATION OF ANTI-CANCER ACTIVITY OF COVALENTLY CONJUGATED METHOTREXATE TO POLYAMIDOAMINE GENERATION 4 DENDRIMER ON MCF-7 CANCER CELLS: AN EXPERIMENTAL STUDY

Background & Aims: Poly (amidoamine) dendrimer (PAMAM) is highly macromolecular at nanosize with widely active amine groups on the surface that allows it to attach to the anti-cancer drugs such as Methotrexate (MTX). This study aimed to synthesize and characterize PAMAM-MTX (dendrimer-MTX) complex, then to evaluate the cytotoxic effect of the synthesized complex on MCF-7 cancer cells. Materials & Methods: To perform this experimental study, initially, MTX was conjugated to the G4 dendrimer using Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), then it w:as char:acterized by Fourier-transform infrared (FTIR) and dynamic light scattering (DLS). Quantitative cellular uptake of nanoparticles was carried out using flow cytometry. The methylthiazol tetrazolium (MTT) and 4′, 6-Diamidino-2-phenylindole dihydrochloride (DAPI) staining assays were used for evaluating the ability of dendrimer-MTX and MTX in inducing cell cytotoxicity and apoptosis on MCF-7 cancer cells, respectively. Results: The results of this study illustrated that the dendrimer-MTX complex had optimal size (30 ± 7.29 nm) and zeta potential (5.35 ± 4.37 mV). Flow cytometry analysis revealed that the cellular uptake was increased (18%) after conjugating MTX on the dendrimer compared to bare dendrimer. Interestingly, cell cytotoxicity and DAPI staining results displayed lower cell cytotoxicity and apoptosis for MCF-7 cells that were treated with dendrimer-MTX compared to free MTX. Conclusion: The obtained data indicated that dendrimer-MTX complex had a higher cellular uptake, but cell cytotoxicity and apoptosis were lower than free MTX.