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

• DOI: 10.1007/s11095-018-2530-2
• Publication Date: 2018-11-08T17:06:51Z
• Authors: Chuhua Xin; Xiuzhong Yao; Bin Du; Weiyu Yang; Liuguo Wang; Lirong Ma; Weiyu Weng
• Keywords: 0301 basic medicine; Chitosan; Drug Carriers; Mice, Inbred ICR; Oligosaccharides; Chitin; Gadolinium; Magnetic Resonance Imaging; 3. Good health; 03 medical and health sciences; Drug Delivery Systems; Neoplasms; Animals; Humans; Nanoparticles; Female; Micelles; Stearic Acids; Chelating Agents

Theranostic 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.Self-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.In 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 T1-weighted MR signal intensity at the tumor region than Magnevist®, and the tumor boundaries were clearly defined for at least 2 h. 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®, the commercially available docetaxel injection, the docetaxel-loaded agent significantly increased the drug concentration in tumor tissue in vivo.The fabricated multifunctional agent may serve as a biodegradable nanoscale MRI contrast agent and as a drug delivery system for tumor diagnosis and treatment.