Plasmon-boosted titanium nitride-based nanoplatform for synergistic photothermal-chemodynamic cancer therapy with smart degradability.

The development of multifunctional nanoplatforms offers promising strategies for advancing cancer treatment, given the generally limited efficacy of single function nanomaterial-based therapeutics. Herein, a plasmon-enhanced "sandwich-like" nanoplatform, titanium nitride@mesoporous silica-iron oxide/polyethylenimine (TiN@mSiO2-Fe3O4/PEI), is designed for synergistic photothermal and chemodynamic therapy (PTT/CDT). The core comprises multiple TiN nanoparticles exhibiting strong plasmon coupling, while the mSiO2 shell is decorated with ultrasmall, surface-exposed Fe3O4 nanozymes (∼3.2 nm) to facilitate catalytic reactions with tumor-associated substrates. Under near-infrared irradiation, the nanoplatform demonstrates a favorable photothermal conversion efficiency (∼39.3 %), making it well-suited for mild-temperature PTT. Meanwhile, the localized heat generated by TiN effectively enhances the catalytic activity of adjacent Fe3O4 nanozymes, thereby promoting hydroxyl radical production and intracellular glutathione depletion. The synergistic photothermal-catalytic interactions within TiN@mSiO2-Fe3O4/PEI result in augmented therapeutic effect by combining efficient PTT with intensified CDT by in situ thermally accelerated Fenton reactions. This is evidenced by >90 % cancer cell killing efficiency in vitro and ∼96 % tumor inhibition rate in MOC1 xenograft models. Moreover, the mSiO2 shell, with its large mesopores, exhibits pH-responsive degradability that enables controlled Fe3O4 release in the acidic tumor microenvironment, which in turn improves therapeutic specificity and reduces systemic toxicity. Collectively, these results demonstrate the potential of TiN@mSiO2-Fe3O4/PEI as a highly effective and versatile nanoplatform for advanced cancer nanotherapy.