Cisplatin and ionic redox pairs co-delivery gelatin/hyaluronic acid hydrogels with amplified chemotherapy/chemodynamic tumor therapy

Abstract

The tumor therapeutic efficacy of cisplatin as a chemotherapy drug and nanomaterial as a chemodynamic inducer are inhibited by the high levels of glutathione (GSH) and hypoxia within the tumor microenvironment. Herein, an injectable nanocomposite hydrogel platform is designed via encapsulating calcined MgMnFe-layered double hydroxide (LDH250) nanosheets and cisplatin into gelatin/hyaluronic acid double-crosslinked hydrogel. As an inducer of Fenton/Fenton-like reactions, LDH250 nanosheets exhibit multiple redox cycling pairs (Mn/Mn/Mn, Fe/Fe) capable of generating abundant reactive oxygen species (ROS), which synergizes with cisplatin to kill tumor cells effectively. Apart from this, the converse reaction of Mn into Mn allows LDH250 to consume GSH and produce O, thereby avoiding the deactivation of ROS and cisplatin, as well as alleviating hypoxia. These characteristics of LDH250 boost the anti-tumor effect of cisplatin and can be enhanced by modulating the calcination temperature. Furthermore, the hydrogels can reduce the transportation distance of ROS in chemodynamic therapy (CDT) and regulate the release of cisplatin. Based on these tactics, the nanocomposite hydrogel platform exhibits effective antitumor efficacy and . This work provides a platform for enhancing the therapeutic efficiency of chemotherapy/CDT by simultaneously depleting GSH and alleviating hypoxia.