乳がんにおける血管新生正常化を促進し、その後のソンダイナミック療法の効果を高める酸素負荷マイクロバブルを用いたデュアルパラメータ逐次超音波照射

The efficacy of sonodynamic ther 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/cm²) to normalize tumor vasculature and alleviates hypoxia, then followed by a sonochemical-activating ultrasound (US_sc, 1.4 W/cm²) 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.