Controlled synthesis of mixed molecular nanostructures from folate and deferrioxamine-Ga(III) on gold and tuning their performance for cancer cells

Abstract

A new strategy is developed for construction of the mixed molecular nanostructures from folic acid (FOA), a targeting agent, and deferrioxamoine-Ga(III), (DFO-Ga(III)), a theranostic agent, on gold-mercaptopropionic acid surface, Au-MPA. The strategy is focused to achieve a system in which all the active constituents of FOA; i.e., pteridine rings, p-aminobenzoeic acid, and the glutamic acid, having high affinity for folate receptor overexpressed on cancer cells; remain unreacted in adjacent to DFO-Ga(III), Au-MPA-[DFO-Ga(III)]‖-[FOA]. For this purpose, the NH₂ groups of FOA and DFO-Ga(III) were attached covalently and separately to COOH of Au-MPA surface allowing all the active groups of FOA to be available for drug delivery purposes. The data obtained through several electrochemical and surface analysis techniques, supported successful construction of the designed mixed molecular nanostructures system. In addition, the results showed that the system is stable, and Ga(III) ion does not leave DFO-Ga(III) complex. The prepared surface was successfully tested for capturing of the breast cancer cells 4T1 as a model. The measurements showed a rapid uptake kinetics (t_1/2 of ~6.0min) and efficient accessibility of the system by the cancer cells; the R_ct was significantly increased in the presence of 4T1 cells compared with blank PBS (ΔR_ct ~420kΩ).

Keywords: Cancer cell; Deferrioxamine-Ga(III); Folic acid; Gold; Mixed nanostructures.