Vitamin E succinate-grafted-chitosan/chitosan oligosaccharide mixed micelles loaded with C-DMSA for Hg2+ detection and detoxification in rat liver

Abstract

Binghui Wei,1,2 Muye He,1,2 Xiaoran Cai,1,2 Xinyu Hou,1,2 Yujie Wang,1,2 Jiaojiao Chen,1,2 Minbo Lan,1 Yanzuo Chen,1,2 Kaiyan Lou,2,3 Feng Gao1,2,41Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, People’s Republic of China; 3State Key Laboratory of Bioengineering Reactor, Shanghai Key Laboratory of New Drug Design and Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, People’s Republic of China; 4Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai 200237, People’s Republic of ChinaCorrespondence: Feng Gao; Kaiyan LouEast China University of Science and Technology, 130 Meilong Road, Shanghai 200237, People’s Republic of ChinaTel [phone]; [phone]Fax [phone]Email [email protected] [email protected]: To determine whether the use of a mixed polymeric micelle delivery system based on vitamin E succinate (VES)-grafted-chitosan oligosaccharide (CSO)/VES-grafted-chitosan (CS) mixed micelles (VES-g-CSO/VES-g-CS MM) enhances the delivery of C-DMSA, a theranostic fluorescent probe, for Hg2+ detection and detoxification in vitro and in vivo.Methods: Mixed micelles self-assembled from two polymers, VES-g-CSO and VES-g-CS, were used to load C-DMSA and afforded C-DMSA@VES-g-CSO/VES-g-CS MM for cell and in vivo applications. Fluorescence microscopy was used to assess C-DMSA cellular uptake and Hg2+ detection in L929 cells. C-DMSA@VES-g-CSO/VES-g-CS MM was then administered intravenously. Hg2+ detection was assessed by fluorescence microscopy in terms of bio-distribution while detoxification efficacy in Hg2+-poisoned rat models was evaluated in terms of mercury contents in blood and in liver.Results: The C-DMSA loaded mixed micelles, C-DMSA@VES-g-CSO/VES-g-CS MM, significantly enhanced cellular uptake and detoxification efficacy of C-DMSA in Hg2+ pretreated human L929 cells. Evidence from the reduction of liver coefficient, mercury contents in liver and blood, alanine transaminase and aspartate transaminase activities in Hg2+ poisoned SD rats treated with the mixed micelles strongly supported that the micelles were effective for Hg2+ detoxification in vivo. Furthermore, ex vivo fluorescence imaging experiments also supported enhanced Hg2+ detection in rat liver.Conclusion: The mixed polymeric micelle delivery system could significantly enhance cell uptake and efficacy of a theranostic probe for Hg2+ detection and detoxification treatment in vitro and in vivo. Moreover, this nanoparticle drug delivery system could achieve targeted detection and detoxification in liver.Keywords: micelles, C-DMSA, mercury poisoning, detection and detoxification, drug delivery system  

Keywords

• micelles
• C-DMSA
• mercury poisoning
• detection and detoxification
• drug delivery system