Titanium boride nanosheets with photo-enhanced sonodynamic efficiency for glioblastoma treatment

Sonodynamic therapy (SDT) has garnered significant attention in cancer treatment, however, the low-yield reactive oxygen species (ROS) generation from sonosensitizers remains a major challenge. In this study, titanium boride nanosheets (TiB₂ NSs) with photo-enhanced sonodynamic efficiency was fabricated for SDT of glioblastoma (GBM). Compared with commonly-used TiO₂ nanoparticles, the obtained TiB₂ NSs exhibited much higher ROS generation efficiency under ultrasound (US) irradiation due to their narrower band gap (2.50 eV). Importantly, TiB₂ NSs displayed strong localized surface plasmon resonance (LSPR) effect in the second near-infrared (NIR II) window, which facilitated charge transfer rate and improved the separation efficiency of US-triggered electron-hole pairs, leading to photo-enhanced ROS generation efficiency. Furthermore, TiB₂ NSs were encapsulated with macrophage cell membranes (CM) and then modified with RGD peptide to construct biomimetic nanoagents (TiB₂@CM-RGD) for efficient blood-brain barrier (BBB) penetrating and GBM targeting. After intravenous injection into the tumor-bearing mouse, TiB₂@CM-RGD can efficiently cross BBB and accumulate in the tumor sites. The tumor growth was significantly inhibited under simultaneous NIR II laser and US irradiation without causing appreciable long-term toxicity. Our work highlighted a new type of multifunctional titanium-based sonosensitizer with photo-enhanced sonodynamic efficiency for GBM treatment. STATEMENT OF SIGNIFICANCE: Titanium boride nanosheets (TiB₂ NSs) with photo-enhanced sonodynamic efficiency was fabricated for SDT of glioblastoma (GBM). The obtained TiB₂ NSs displayed strong localized surface plasmon resonance (LSPR) effect in the second near-infrared (NIR II) window, which facilitated charge transfer rate and improved the separation efficiency of US-triggered electron-hole pairs, leading to photo-enhanced ROS generation efficiency. Furthermore, TiB₂ NSs were encapsulated with macrophage cell membranes (CM) and then modified with RGD peptide to construct biomimetic nanoagents (TiB₂@CM-RGD) for efficient blood-brain barrier (BBB) penetrating and GBM targeting. After intravenous injection into the tumor-bearing mouse, TiB₂@CM-RGD can efficiently cross BBB and accumulate in the tumor sites. The tumor growth was significantly inhibited under simultaneous NIR II laser and US irradiation without causing appreciable long-term toxicity.