Work

Dual-parameter sequential ultrasound irradiation with oxygen-loaded microbubbles induces vascular normalization to potentiate sonodynamic therapy in breast cancer

Year: 2026

Type: article

Abstract: The efficacy of sonodynamic therapy (SDT) for breat cancer is limited by tumor hypoxia and the constrained bio-effects of single-parameter ultrasound. To address this, an optimized SDT strategy was established with microbubbles loaded with Chlorin e6 (Ce6) and oxygen (CMO) and a dual-parameter sequential ultrasound irradiation mode, which begins with a cavitation-inducing ultrasound (US ca , 0.6 W/cm 2 ) to normalize tumor vasculature and alleviates hypoxia, then followed by a sonochemical-activating ultrasound (US sc , 1.4 W/cm 2 ) to elicit potent tumor cell killing effect. It was demonstrated by cellular experiments that US ca facilitated the release of oxygen and Ce6, allowing US sc to exert maximal cytotoxicity effect. In vivo, US ca pretreatment was indispensable for normalizing tumor vasculature, while US sc alone was found to be vasculature-damaging. With the synergistic effect of sequential US ca and US sc ultrasound irradiation, superior anti-tumor effect was achieved, manifested as a 75% reduction in tumor volume and significant outperformance over classical SDT mode. Overall, This work pioneers a dual-stage sequential ultrasound irradiation mode that tactically induces vascular nonmalization as a sensitizing step for subsequent SDT, culminating in a novel SDT strategy with high translational potential.

Source: Materials Today Bio

DOI: 10.1016/j.mtbio.2026.102777