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

Excessive reducrtionb of glutathione (GSH restricte chemodynamic therapy (CDT) efficacy through the consumption of ·OH. Hence, the design of nano-systems to consume GSH is one effective method to enhance CDT efficacy.

In a new study published in Glycoscience & Therapy, a team of researchers in China used β-cyclodextrin grafted hyaluronic acid (HA-CD) as host moieties to include ferrocene-arylboronic acid conjugate (Fc-BA) through host-guest inclusion. This allows the further binding of curcumin to form supramolecular self-assemblies with active targeting ability and tumor micro-environment stimuli-responsive behavior.

The team presented a method for preparing supramolecular prodrug assemblies (SPSAs) using the host-guest interaction between β-cyclodextrin grafted hyaluronic acid (HA-CD) and ferrocene-arylboronic acid conjugate (Fc-BA) for GSH-augmented therapeutic potency of CDT.

"Fc could catalyze H₂O₂ 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,“ explains corresponding author Yang Bai. "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.

“This work introduces a supramolecular self-assembly with dual functions of GSH-synthesis inhibition and -consumption for efficient enhancing chemodynamic therapy,” adds Bai. “The combination of the BA-induced GSH consumption and Cur-induced inhibition of TrxR activation could achieve the simultaneously release of dual functional molecules from self-assembly for augmented CDT.”
 

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Contact the author: Yang Bai, College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi’an, 710021, China, baiyang@sust.edu.cn

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