Therapeutic effect of deferrioxamine conjugated to PEGylated gold nanoparticles and complexed with Mn(II) beside the CT scan and MRI diagnostic studies

Abstract

Synthesis, characterization, and in-vitro/in-vivo examinations of a theranostic system with novel formulation and straightforward synthesis method are reported in this work. Deferrioxamine-manganese(II), as a theranostic complex (Deferrioxamine as therapeutic and manganese(II) as MRI imaging agent) is conjugated in adjacent to folic acid with the PEGylated gold nanoparticles, leading to formation of biodegradable and biocompatible AuNPs-PEG-DFO-Mn(II)parallel to-FOA system. The fabrication process is followed by several characterization methods including TEM, DLS, xi-potential, FTIR, XPS, UV-vis, and fluorescence. Initially, the characterized system was tested as a contrast agent by MRI and X-ray CT-scan techniques. The values obtained for relaxation rate and the slope of Hounsfield unit vs. concentration, 12.0 mM(-1) s(-1) and 8.27 HU L/g, supported efficiency of the system for dual imaging applications. In addition, an obvious T1-weighed contrast was observed by in-vivo method. The intracellular delivery of the system was monitored by flow cytometry and florescence microscopy imaging based on PI florescent dye attached to the AuNPs as AuNPs-PEG-PIparallel to-FOA. Then, anticancer activity of the system was evaluated by in-vivo experiments carried out on the 4T1 breast tumor-bearing BALB/c mice. Biodistribution of the system was assessed by ICP-OES measurements, indicating effective accumulation of the system in breast tumors. Further experiments exhibited that the growth and metastasis of tumor were significantly inhibited by the system, which in turn, was found to be correlated with therapeutic effect of DFO. Besides abovementioned interesting aspects, this is the first report explaining the dual effects of DFO; (i) complexing capability for contrast agents and (ii) therapeutic effect for 4T1 cancer cells. Finally, biocompatibility of the system was confirmed by blood biochemistry and histopathological evaluations.