Self-augmented catabolism mediated by Se/Fe co-doped bioceramics boosts ROS storm for highly efficient antitumor therapy of bone scaffolds.

Abstract

The overexpression of glutathione (GSH) within the tumor microenvironment has long been considered as the major obstacle for reactive oxygen species (ROS)-based antitumor therapies. To address this challenge, a selenite (SeO₃^2 -) and ferric ion co-doped hydroxyapatite (SF-HAP) nanohybrid was synthesized, which is then introduced into poly-L-lactic acid (PLLA) to prepare porous scaffold by selective laser sintering to continuously release Fe³⁺ and SeO₃^2- ions. Of great significance is the released SeO₃^2- catabolize GSH to generate superoxide anion (O₂^•-) rather than directly eliminating GSH, thereby reversing the obstacle posed by its overexpression and achieving a "waste-to-treasure" transformation. The newly generated O₂^•- synergizes with the hydroxyl radicals (•OH) produced by the Fenton reaction between Fe^3+/2+ and hydrogen peroxide, triggering high concentration ROS storms. Collectively, the PLLA/SF-HAP scaffold mediated self-augmented catabolism dynamic progress significantly raised intracellular ROS levels, almost twice as much as PLLA/Fe-HAP scaffold, thereby effectively inducing tumor cell apoptosis. The study provides an innovative inspiration for ROS-based antitumor therapies.