Chuhua Xin1, Xiuzhong Yao2, Bin Du1, Weiyu Yang1, Liuguo Wang1, Lirong Ma1, Weiyu Weng3,4. 1. Department of Pharmaceutical Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China. 2. Department of Radiology, Zhongshan Hospital Affiliated to Fudan University, Shanghai, People's Republic of China. 3. Department of Pharmaceutical Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China. wyweng@ecust.edu.cn. 4. Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai, People's Republic of China. wyweng@ecust.edu.cn.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The fabricated multifunctional agent may serve as a biodegradable nanoscale MRI contrast agent and as a drug delivery system for tumor diagnosis and treatment.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The fabricated multifunctional agent may serve as a biodegradable nanoscale MRI contrast agent and as a drug delivery system for tumor diagnosis and treatment.
Entities:
Keywords:
biocleavable gadolinium chelates; drug delivery; nanomicelle system; tumor imaging
Authors: Juan L Vivero-Escoto; William J Rieter; Honam Lau; Rachel C Huxford-Phillips; Wenbin Lin Journal: Small Date: 2013-04-24 Impact factor: 13.281