Author/Authors :
Ma, Lirong Engineering Research Center of Pharmaceutical Process Chemistry - Ministry of Education - School of Pharmacy - East China University of Science and Technology, Shanghai, China , Yang, Weiyu Engineering Research Center of Pharmaceutical Process Chemistry - Ministry of Education - School of Pharmacy - East China University of Science and Technology, Shanghai, China , Wu, Dingmei Engineering Research Center of Pharmaceutical Process Chemistry - Ministry of Education - School of Pharmacy - East China University of Science and Technology, Shanghai, China , Jiang, Mengmeng Department of Radiology - Zhongshan Hospital Affiliated to Fudan University, Shanghai, China,200032, PR China , Yao, Xiuzhong Department of Radiology - Zhongshan Hospital Affiliated to Fudan University, Shanghai, China , Weng, Weiyu Department of Radiology - Zhongshan Hospital Affiliated to Fudan University - Shanghai, China,200032, PR China
Abstract :
There is a strong need to develop MRI contrast agents (CAs) with lower in vivo retention, stronger signal enhancement, and more specific imaging. Here, we report a novel dextran (DEX)-based nanomicelle system as an MRI CA with superior tumor imaging and relatively short intravascular persistence. Gadolinium (Gd)-chelate (DTPA-Gd) was conjugated directly to DEX hydroxyl via a degradable ester bond. DEX-DTPA-Gd was then modified with dodecylsuccinic anhydride to obtain the amphiphilic derivative, 2-dodecylsuccinic acid (DSA)-grafted DEX-DTPA-Gd. Nanomicelles were prepared by dissolving DSA-DEX-DTPA-Gd in water using ultrasonication. The physicochemical properties, cytotoxicity, and MRI efficiency of the synthesized CA were evaluated. The synthesized DSA-DEX-DTPA-Gd self-assembled into nanomicelles with an average diameter of 67.80 ± 5.21 nm. Within the given Gd concentration range, DSA-DEX-DTPA-Gd and Magnevist® exhibited similar cytotoxicity. DEX-based CAs resulted in a greater contrast enhancement of T1-weighted signal intensity in the tumor region than Magnevist®, and the tumors were clearly defined for at least 3 h. Simultaneously, the ester bond in DSA-DEX-DTPA-Gd facilitated the elimination of Gd chelates, compared with the relatively more stable amide linker. The DEX-based nanomicelle system with directly ester-bound DTPA-Gd may serve as an MRI CA with superior tumor imaging and relatively rapid elimination
Keywords :
Dextran , Nanomicelle system , Biocleavable gadolinium chelates , Tumor imaging , Elimination
