Chitosan modified with gadolinium diethylenetriaminepentaacetic acid for magnetic resonance imaging of DNA/chitosan nanoparticles

We have prepared chitosan (CH)–gadolinium (Gd) diethylenetriaminepentaacetic acid (DTPA) conjugates that have potential as contrast agents for magnetic resonance imaging. Conjugates were synthesized starting with low molecular weight chitosan (25 kDa and 96% degree of deacetylation (noted DDA)) by covalent linkage of DTPA to chitosan amine groups confirmed by Fourier transform infrared spectroscopy (FTIR). Different DTPA/amine ratios were used to obtain different degrees of DTPA conjugation (10–20%), determined by nuclear magnetic resonance (1H NMR) spectroscopy, a colorimetric assay, and isothermal titration calorimetry (ITC). After preparation of chitosan–DTPA complexes with Gd, polyelectrolyte complexes were assembled with plasmid DNA pEGFPLuc (6367 bp) and investigated using scanning electron microscopy and scanning transmission electron microscopy. Particles were spherical with diameters in the range of 30–150 nm. The presence of gadolinium in the nanoparticles was confirmed by energy dispersive X-ray spectroscopy. Gd was located preferentially in a 2–5 nm wide area surrounding the nanoparticles.