Specific lipase-responsive polymer-coated gadolinium nanoparticles for MR imaging of early acute pancreatitis

• Published in: Biomaterials 2014-01, Vol.35 (1), p.356-367
• Main Authors: Zhang, Hong-Wu, Wang, Li-Qin, Xiang, Qing-Feng, Zhong, Qian, Chen, Lu-Ming, Xu, Cai-Xia, Xiang, Xian-Hong, Xu, Bo, Meng, Fei, Wan, Yi-Qian, Deng, David Y.B
• Format: Article
• Language: English
• Subjects: Acute Disease; Acute pancreatitis; Advanced Basic Science; Animals; Conditional activation; Dentistry; Diagnosis; Early Diagnosis; Gadolinium; Gadolinium - chemistry; HEK293 Cells; Humans; Lipase - metabolism; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Microscopy, Electron, Transmission; Nanoparticle; Nanoparticles; Pancreatitis - diagnosis; Polymers; Rats; Rats, Sprague-Dawley
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.09.046

Abstract Currently, available methods for diagnosis of acute pancreatitis (AP) are mainly dependent on serum enzyme analysis and imaging techniques that are too low in sensitivity and specificity to accurately and promptly diagnose AP. The lack of early diagnostic tools highlights the need to search for a highly effective and specific diagnostic method. In this study, we synthesized a conditionally activated, gadolinium-containing, nanoparticle-based MRI nanoprobe as a diagnostic tool for the early identification of AP. Gadolinium diethylenetriaminepentaacetic fatty acid (Gd-DTPA-FA) nanoparticles were synthesized by conjugation of DTPA-FA ligand and gadolinium acetate. Gd-DTPA-FA exhibited low cytotoxicity and excellent biocompatibility when characterized in vitro and in vivo studies. L-arginine induced a gradual increase in the intensity of the T1-weighted MRI signal from 1 h to 36 h in AP rat models. The increase in signal intensity was most significant at 1 h, 6 h and 12 h. These results suggest that the Gd-DTPA-FA as an MRI contrast agent is highly efficient and specific to detect early AP.