(AGENPARL) – LONDON (UNITED KINGDOM), gio 10 settembre 2020
Active targeting strategy had achieved inspiring progress for drug accumulation in tumor therapy, however, the insufficient expression level of many potential receptors posed challenges for drug delivery. Poly-γ-glutamic acid (γ-pGluA), a naturally occurring anionic biopolymer, showed high affinity with Tumor-associated gamma-glutamyl transpeptidase (GGT), which localized on the cell-surface and exhibited intracellular redox homeostasis-dependent expression pattern, thus the GGT was utilized for mediating endocytosis of the nanoparticles. Herein, a GGT-targeting nanopolyplexes (γ-pGluA-CSO@Fe3+, PCFN) consisted of cationic chitosan (CSO) and GGT-targeting γ-pGluA blended with iron ion were constructed to load Reactive oxygen species (ROS)-induced menadione (MA) and doxorubicin (DOX), which was utilized to investigate the mechanism of GGT up-regulation. Briefly, the pre-treated PCFN/MA induced intracellular oxidative stress environment, which facilitated adjusted up-regulated GGT expression and boosted tumor targeting. Subsequently, the destroyed redox homeostasis sensitized tumor for synergistic therapy. The innovative strategy of augmenting active targeting by disturbing intracellular redox homeostasis offer enlightenment for the application of γ-pGluA-derived nanopolyplexes.
You have access to this article