In vitro and in silico characteristics of doxorubicin-loaded four polymeric-based polysaccharides-modified super paramagnetic iron oxide nanoparticles for cancer chemotherapy and magnetic resonance imaging

Super Paramagnetic Iron Oxide Nanoparticles have attracted much attention in drug delivery systems because of their considerable surface-to-volume ratio and content as well. In this regard, in this study, four different formulations of magnetic nanoparticles were synthesized via various polymeric coating layer (beta-cyclodextrin, Chitosan, Gum Arabic, and Alginate) in order to find an appropriate polymer in terms of higher drug loading efficiency and capacity. Molecular dynamics simulation and Quantum mechanics were manipulated to examine the interaction mechanism between the polysaccharide polymers and Doxorubicin. Based on the calculated results, As the best candidate, beta CD was chosen for DOX loading. DOX, a hydrophilic drug, was loaded into each of the four formulations. The optimum formulation, Fe3O4-beta CD, possessed loading efficiency and capacity, with 97% and 13%, respectively. The selected nanocarrier was fully characterized by Fourier Transform Infrared, VSM, TGA, XRD, SEM, UV-Vis, DLS, and TEM. TEM result exhibited the prepared Fe3O4-beta CD-DOX nanoparticles had a spherical shape (core and shell) and the size of around 15 nm. In vitro release investigation was conducted using HPLC analysis in the phosphate-buffered saline in acidic (pH=5.4) and neutral (pH=7.4) medium. The obtained results demonstrated that a sustain release performance for more than 72 h with the amount of 50% DOX release in pH=5.4. Cytotoxicity assay showed the toxicity of bare Fe3O4 and Fe3O4-beta CDNPs against MDA-MB468 cancerous cell and MCF10A normal cell was negligible and DOX-loaded NPs (Fe3O4-beta CD-DOX) illustrated a higher toxicity in MDA-MB468 cancerous cells than MCF 10 A normal cells. The results showed that Fe3O4-beta CD-DOXNPs could improve the therapeutic efficacy and also reduce the adversarial effects; accordingly, the prepared system could be served as a promising drug delivery system in cancer treatment.

Automated summary

Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) have gained significant attention in drug delivery systems due to their high surface-to-volume ratio and content. This study aimed to synthesize four different formulations of magnetic nanoparticles coated with various polymeric layers to find the most suitable polymer for higher drug loading efficiency and capacity. Molecular dynamics simulation and quantum mechanics were used to investigate the interaction mechanism between polysaccharide polymers and Doxorubicin (DOX). The results showed that Fe3O4-beta CD-DOX nanoparticles had a spherical shape and a size of around 15 nm. In vitro release investigation demonstrated sustained release performance for more than 72 hours in an acidic medium. Cytotoxicity assay revealed that Fe3O4-beta CD-DOX nanoparticles exhibited higher toxicity in cancer cells compared to normal cells. Overall, the prepared system showed promise as a drug delivery system for cancer treatment.