Development of Gd(III) porphyrin-conjugated chitosan nanoparticles as contrast agents for magnetic resonance imaging

A novel magnetic resonance imaging (MRI) contrast agent based on gadolinium meso-tetrakis(4-pyridyl)porphyrin [Gd(TPyP)] conjugated with chitosan nanoparticles has been developed. The chitosan nanoparticles were synthesized following an ionic gelation method and the conditions optimized to generate small nanoparticles (CNs) with a narrow size distribution of 35-65 nm. The gadolinium meso-tetrakis(4-pyridyl)porphyrin [Gd(TPyP)] was loaded into chitosan nanoparticles by passive adsorption. The interaction of chitosan with Gd(TPyP) has been examined by UV-visible, Fourier transform infrared spectroscopies (FT-IR) and inductively coupled plasma mass spectrometry (ICP-MS), which indicate the successful association of Gd(TPyP) without any structural distortion throughout the chitosan nanoparticles. The potential of Gd(TPyP)CNs as MRI contrast agent has been investigated by magnetic resonance imaging (MRI) in-vitro. Relaxivities of Gd(TPyP)-CNs obtained from T-1-weighted images, increased with Gd concentration and attained an optimum T-1 of 38.35 mM(-1) s(-1), which is 12-fold higher compared to commercial Gd-DOTA (similar to 4 mM(-1) s(-1) at 3T). The combination of such strong MRI contrast with the known properties of porphyrins in photodynamic therapy and biocompatibility of chitosan, presents a new perspective in using these compounds in cancer theranostics. (C) 2015 Elsevier B.V. All rights reserved.