Vitamin E succinate-grafted-chitosan/chitosan oligosaccharide mixed micelles loaded with C-DMSA for Hg2+ detection and detoxification in rat liver
Vitamin E succinate-grafted-chitosan/chitosan oligosaccharide mixed micelles loaded with C-DMSA for Hg2+ detection and detoxification in rat liver
Blog Article
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 7201 diablosport predator 2 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 +86 21 6425 2449; +86 21 6425 3299Fax +86 21 6425 8277Email [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, greenlee 45300 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 .