ABSTRACT
Objective To prepare gadolinium-loaded stearic acid grafted chitooligosaccharide (COSSA-DTPA-Gd) and evaluate its micelle properties,cytotoxicity,relaxation rate in vitro,and pancreatic tumor in vivo imaging.Methods Stear ic acid grafted chitooligosaccharide (COSSA) was synthesized by acetylation reaction between stearic acid and chitooligosaccharide.Diethylenetriaminepentaacetic dianhydride (DTPA) was conjugated to the residual amino groups of COSSA,then Gd3+ was chelated to obtain the final product.The micelle properties were measured using an electron microscopy and a laser particle sizer.The MTT assay was adopted to determine cytotoxicity.The in vitro relaxation rate and in vivo imaging of pancreatic tumor were evaluated using an MR scanner.Results COSSA-DTPA-Gd could self-assemble into stable micelles in aqueous solutions with a critical micelle concentration of (5.12±0.43)μg/ml.The micelles had positive charge and exhibited roughly spherical shape with a mean diameter of (58.3± 5.7)nm.The content of Gd3+ in COSSA-DTPA-Gd was 330.31 μmol/g.The nanoprobe and Magnevist,the commercial formulation,showed similar cytotoxicity (P＞0.05).The cell survival rate within 24 h were higher than 85％.The in vitro relaxation rate of COSSA-DTPA-Gd was 8.23 mM-1 ·s-1.After intravenous injection,COSSA-DTPA-Gd showed a better positive contrast-enhancing effect for pancreatic tumor than Magnevist.The MR images at the tumor periphery was rapidly enhanced,while a slow increase in image quality was observed in tumor core.Conclusion The prepared COSSA-DTPA-Gd can be used for efficient MR imaging of pancreatic tumor.