Biomimic Binding Affinity Gradients Triggered GSH-Response of Core-Shell Nanoparticles for Cascade Chemo/Chemodynamic Therapy

In eukaryotes and prokaryotes, some copper transportations driven by gradient copper-binding affinities exhibit typical glutathione (GSH)-responsive features. Inspired by these delicate endogenous processes, a biomimic copper-ion mediated GSH-responsive nanomedicine is designed based on the gradient copper-binding strengths between polydopamine (PDA) species and GSH. The nanomedicine is constructed as core-shell nanoparticles with copper-polydopamine (Cu-PDA) coordinated shell and micellar core encapsulating chemotherapeutic drug of beta-lapachone (beta-lapa). In tumor cells, the excess intracellular GSH will reduce and extract the Cu(II) from the Cu-PDA network, triggered by the binding affinity gradients between Cu-PDA and Cu-GSH, resulting in the breaking of the shell and the releasing of beta-lapa and Fenton agent copper. The additional Fenton reaction of copper ions induces excess oxidative damage of tumor cells assisted by the abundant H2O2 amplified by beta-lapa, achieving cascade anticancer effects combining chemodynamic therapy with chemotherapy. This multilevel anticancer system exhibits an efficient tumor inhibitory rate and a negligible systematic toxicity for normal organs in vivo, presenting a new bioinspired GSH-responsive strategie to develop stimuli-responsive structures.

Automated summary

The biomimetic copper-ion mediated GSH-responsive nanomedicine exploits the gradient copper-binding strengths between polydopamine and GSH to release chemotherapeutic drugs specifically in tumor cells, achieving cascade anticancer effects. This multilevel anticancer system demonstrates efficient tumor inhibition with minimal systemic toxicity, presenting a new bioinspired GSH-responsive strategy for developing stimuli-responsive structures.