Vacancy-engineered Mn-doped iron oxide nano-crystals for enhanced sonodynamic therapy through self-supplied oxygen

Sonodynamic therapy (SDT) is a minimally invasive therapeutic approach, that uses ultrasound activating sonosensitizers to generate reactive oxygen species (ROS) for inducing the tumor cell death. However, the SDT is always limited by the dissatisfactory performance of sonosensitizers and hypoxic tumor microenvironment (TME). Nano iron oxide is a narrow bandgap semiconductor material with good biocompatibility. The doping of manganese into iron oxide (Mn-doped iron oxide nano-crystals named Mn-Fe₂O₃ NCs) not only reduced the band gap of iron oxide and altered the valence band position of iron oxide, but also introduced more oxygen vacancies and inhibited the complexation of electrons (e^-) and holes (h⁺), significantly enhancing the ability to generate ROS. The Mn-Fe₂O₃ NCs improved the hypoxic TME by self-generating oxygen and consuming endogenous glutathione (GSH), which amplified oxidative stress and further enhanced the SDT. The therapeutic results showed that the prepared Mn-Fe₂O₃ NCs could efficiently inhibit the triple-negative breast cancer (TNBC) cells by SDT (80.49 % inhibition ratio in vivo). Overall, we propose a simple method to design inorganic sonosensitizers for enhancing efficient sonodynamic therapy.