文献类型：期刊文献

英文题名：Stearic Acid-Grafted Chitooligosaccharide Nanomicelle System with Biocleavable Gadolinium Chelates as a Multifunctional Agent for Tumor Imaging and Drug Delivery

作者：Xin, Chuhua[1];Yao, Xiuzhong[2];Du, Bin[1];Yang, Weiyu[1];Wang, Liuguo[1];Ma, Lirong[1];Weng, Weiyu[1,3]

机构：[1]East China Univ Sci & Technol, Dept Pharmaceut Engn, Sch Pharm, Shanghai, Peoples R China;[2]Fudan Univ, Zhongshan Hosp, Dept Radiol, Shanghai, Peoples R China;[3]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China

年份：2019

卷号：36

期号：1

外文期刊名：PHARMACEUTICAL RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000449754400004)】；

基金：TThis work was supported by the Shanghai Natural Science Foundation (16ZR1405900). The authors thank the staff of the Center of Analysis & Test at East China University of Science and Technology for helping with the ICP-OES measurement.

语种：英文

外文关键词：biocleavable gadolinium chelates; drug delivery; nanomicelle system; tumor imaging

摘要：PurposeTheranostic nanoplatforms are promising approaches for diagnosis and treatment. Here, we report a drug-loaded nanomicelle system with biocleavable gadolinium (Gd) chelates as a multifunctional biodegradable agent for simultaneous magnetic resonance imaging (MRI) and drug delivery.MethodsSelf-assembled nanomicelles based on stearic acid-grafted chitooligosaccharide were utilized as vehicles. Gd chelates, DTPA-Gds, were linked to the nanomicelles via redox-responsive disulfide bonds, and hydrophobic drugs were encapsulated in the micelle cores. MRI and cargo delivery were investigated in orthotopic pancreatic tumor-bearing mice.ResultsIn vivo MRI demonstrated that the biodegradable agent was cleaved by endogenous thiols after intravenous injection, and the released DTPA-Gds were eliminated rapidly. At the same time, the agent resulted in a greater contrast enhancement of T-1-weighted MR signal intensity at the tumor region than Magnevist (R), and the tumor boundaries were clearly defined for at least 2h. In addition, the agent possessed high drug-loading and tumor-targeting capacities. Loading content and encapsulation efficiency of docetaxel were 3.2% and 99.4%, respectively. Compared with Taxotere (R), the commercially available docetaxel injection, the docetaxel-loaded agent significantly increased the drug concentration in tumor tissue in vivo.ConclusionThe fabricated multifunctional agent may serve as a biodegradable nanoscale MRI contrast agent and as a drug delivery system for tumor diagnosis and treatment.