Glioblastoma (GBM) is a deadly
brain tumor with poor prognosis and high mortality in patients. Given the low efficacy and serious side effects of current GBM
therapy compared to those of conventional surgery,
chemotherapy and
radiation therapy, the development of a novel method for GBM management is very urgent. Sonodynamic
therapy (SDT) has gained considerable attention in GBM
therapy due to the advantages of deep tissue penetration and high biosafety. However, the low
reactive oxygen species (ROS) generation efficacy of SDT has generally limited further applications and clinical translation. In this work, we report the simultaneous application of focused ultrasound-induced moderate thermal treatment (42 °C) and SDT for synergistic enhancement against GBM.
Manganese ion (Mn2+)-chelated
human serum albumin (HSA)-
chlorin e6 (Ce6) nanoassemblies (HCM
NAs) as targeting nanosonosensitizers were prepared using an assembly strategy. Our studies indicated that the HCM
NAs had excellent T1-weighted contrast performance (12.2 mM-1 s-1) compared to that of clinically used
Magnevist (4.3 mM-1 s-1) and achieved highly selective in vitro cell recognition and in vivo
tumor-targeting magnetic resonance (MR) and fluorescence (FL) imaging with a signal-to-background ratio of 13.5 at 24 h post injection. Upon imaging-guided focused ultrasound irradiation, the temperature and
reactive oxygen species (ROS) content of the
tumor region increased simultaneously over time, achieving synergistic effects. The
brain tumors were completely suppressed in subcutaneous mouse models of
glioma, and the antitumor effect was greatly improved in orthotopic mouse models of
glioma. It suggest that the synergistic treatment with moderate temperature and SDT induced by imaging-guided focused ultrasound is a promising platform against GMB, holds great potential in clinical settings.