Self-assembled magnetic resonance imaging nanoprobes based on arachidyl chitosan for cancer diagnosis

摘要

Arachidyl chitosan (chitosan oligosaccharide-arachidic acid; CSOAA)-based self-assembled nanoprobes for magnetic resonance imaging (MRI) of neoplastic lesions was developed and evaluated in vitro. Diethylenetriaminepentaacetic dianhydride (DTPA) was conjugated to chitosan oligosaccharide (CSO) and Gd3+ was chelated to the resulting ligand. DTPA conjugation and Gd3+ chelation were confirmed primarily by Fourier transform infrared spectroscopy (FT-IR) and zeta potential measurement. A spherical nanoprobe of around 150nm mean diameter in the tested concentration range was formed in an aqueous environment by simple dissolution. The critical aggregation concentration (CAC) of the CSOAA-based nanoprobe was 3.86μg/ml, indicating its stability after dilution in body fluid. The nanoprobe had negligible toxicity in head and neck cancer cell lines (Hep-2 and FaDu cells). The amount of Cy5.5-labeled nanoprobe taken-up by cells, as observed by confocal laser scanning microscopy (CLSM), increased according to incubation time (up to 12h). A phantom study showed a T_1-positive contrast-enhancing effect of the developed CSOAA-based nanoprobe, compared to that of the commercial formulation (Gd-DTPA; Magnevist). These results indicate that the CSOAA-based nanoprobe can be used for efficient MR imaging of neoplastic cells.