A supramolecular self-assembly with dual functions of GSH-synthesis inhibition and -consumption for efficient enhancing chemodynamic therapy

Abstract

The excessive reduced GSH obviously restrict the chemodynamic therapy (CDT) efficacy through the consumption of ·OH. Therefore, the design of nano-systems to consume GSH is one effective method to enhance CDT efficacy. In this paper, β-cyclodextrin grafted hyaluronic acid (HA-CD) is utilized as host moieties to include ferrocene-arylboronic acid conjugate (Fc-BA) through host-guest inclusion, further binding curcumin to form supramolecular self-assemblies with active targeting ability and tumor micro-environment stimuli-responsive behavior. Fc could catalyze H 2 O 2 to generate ·OH through Fenton reaction, and curcumin could be released under acidic pH to realize the consumption of GSH and inhibition of thioredoxin reductase, reducing the biosynthesis of GSH. Based on this strategy, the over-expressed GSH levels in tumor can be effectively consumed to achieve satisfied CDT outcome. In vitro and in vivo experiments suggested that this GSH-synthesis inhibition and -consumption strategy can significantly amplify cellular oxidative stress for excellent CDT efficacy.