Four Birds with One Stone: A Bandgap-Regulated Multifunctional Schottky Heterojunction for Robust Synergistic Antitumor Therapy upon Endo-/Exogenous Stimuli

Considering the profound impact of structure on heterojunction catalysts, the rational design of emerging catalysts with optimized energy band structures is required for antitumor efficiency. Herein, we select titanium nitride (TiN) and Pt to develop a multifunctional Schottky heterojunction named Pt/H-TiN&SRF (PHTS) nanoparticles (NPs) with a narrowed bandgap to accomplish "four birds with one stone" involving enzyo/sono/photo three modals and additional ferroptosis. The <i>in situ</i>-grown Pt NPs acted as electron traps that can cause the energy band to bend upward and form a Schottky barrier, thereby facilitating the separation of electron/hole pairs in exogenous stimulation catalytic therapy. In addition, endogenous catalytic reactions based on peroxidase (POD)- and catalase (CAT)-mimicking activities can also be amplified, triggering intense oxidative stress, in which CAT-like activity decomposes endogenous H₂O₂ into O₂ alleviating hypoxia and provides reactants for sonodynamic therapy. Moreover, PHTS NPs can elicit mild photothermal therapy with boosted photothermal properties as well as ferroptosis with loaded ferroptosis inducer sorafenib for effective tumor ablation and apoptosis-ferroptosis synergistic tumor inhibitory effect. In summary, this paper proposes an attractive design for antitumor strategies and highlights findings for heterojunction catalytic therapy with potential in tumor theranostics.