The technology was developed by researchers at the Nanomaterials Laboratory, Chemistry Department, Indian Institute of Technology, Kharagpur, India. It is based on the fact that the effective conjugation of folic acid on the surface of superparamagnetic iron oxide nanoparticles (SPION) enables their high intracellular uptake by cancer cells. The researchers have demonstrated that hydrophilicity of the surface modifier greatly influences the stability of the folate conjugate system in aqueous media. The judicious selection of surface-coupling molecules controls the agglomeration of SPION-folate conjugates in biological environments, enabling its increased efficacy.

In this work, magnetite nanoparticles were surface modified with 2-carboxyethyl phosphonic acid to form a highly stable aqueous dispersion of magnetic particles. These carboxyl group functionalized particles were coupled with folic acid and fluorescein isothiocyanate through 2,2-(ethylenedioxy) bis-ethylamine – a hydrophilic linker using carbodiimide. Such magnetic nanoparticle-folate conjugate particles are stable for a long time over a wide biological pH range. These folic acid-conjugated magnetic particles show high intracellular uptake by B16F0 and HeLa cancer cell lines. Additionally, such particles show remarkably low phagocytosis as verified by taking peritoneal macrophages.