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

AIM

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 Hg 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 Hg detection in L929 cells. C-DMSA@VES-g-CSO/VES-g-CS MM was then administered intravenously. Hg detection was assessed by fluorescence microscopy in terms of bio-distribution while detoxification efficacy in Hg-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 Hg pretreated human L929 cells. Evidence from the reduction of liver coefficient, mercury contents in liver and blood, alanine transaminase and aspartate transaminase activities in Hg poisoned SD rats treated with the mixed micelles strongly supported that the micelles were effective for Hg detoxification in vivo. Furthermore, ex vivo fluorescence imaging experiments also supported enhanced Hg detection in rat liver.

CONCLUSION

The mixed polymeric micelle delivery system could significantly enhance cell uptake and efficacy of a theranostic probe for Hg detection and detoxification treatment in vitro and in vivo. Moreover, this nanoparticle drug delivery system could achieve targeted detection and detoxification in liver.