The further bioapplications of sonodynamic therapy (SDT)
were hindered
by the inadequate efficiency and poor degradability of sonosensitizers
and the hypoxic tumor microenvironment (TME). Therefore, it is ideal
to develop pH-sensitive sonosensitizers that generate abundant reactive
oxygen species (ROS) and rapidly degrade in a neutral environment
while slowly degrading in an acidic environment to reduce their long-term
toxicity. Herein, the defective tungsten oxide nanobelts (WO
x
NBs) were developed as a type of pH-sensitive and
biodegradable sonosensitizers with a high SDT efficiency and low toxicity
for enhanced SDT. The defective oxygen sites of WO
x
NBs could inhibit the recombination of electrons and holes,
making WO
x
NBs promising sonosensitizers
that could generate abundant ROS under ultrasound (US) irradiation.
Enhanced by the catalase (CAT) that reacted with H2O2 to generate O2, the WO
x
NBs exhibited better SDT performance against 4T1 cells in both normoxic
and hypoxic environments. In addition, the WO
x
NBs could degrade by releasing protons (H+), resulting
in intracellular acidification and inhibited cell motility that further
enhanced the therapeutic effects of SDT. Assisted with CAT and ALG
for hypoxia refinement and better retention, the WO
x
NBs enabled effective SDT and antimetastasis against 4T1 tumors in vivo. Most importantly, the WO
x
NBs could degrade rapidly in normal tissues but slowly in
an acidic TME, which was favorable for their fast clearance, without
any obvious long-term toxicity. Our work developed defective WO
x
NBs with a high SDT efficiency and pH-sensitive
degradation for enhanced SDT, which extended the biomedical application
of tungsten-based nanomaterials and the further development of SDT.