Concurrent anti-vascular therapy and chemotherapy in solid tumors using drug-loaded acoustic nanodroplet vaporization

摘要: Drug-loaded nanodroplets (NDs) can be converted into gas bubbles through ultrasound (US) stimulation, termed acoustic droplet vaporization (ADV), which provides a potential strategy to simultaneously induce vascular disruption and release drugs for combined physical anti-vascular therapy chemotherapy. Doxorubicin-loaded NDs (DOX-NDs) with mean size of 214 nm containing 2.48 mg DOX/mL were used in this study. High-speed images displayed bubble formation cell debris, demonstrating the reduction viability after ADV. Intravital imaging provided direct visualization disrupted tumor vessels (vessel <30 μm), extravasation distance was 12 μm DOX-NDs group increased over 100 μm DOX-NDs + US group. Solid perfusion on US significantly reduced 23% vaporization, but gradually recovered 41%, especially at periphery 24 h. Histological revealed tissue necrosis, large amount drug extravasation, disruption, immune infiltration center. Tumor sizes decreased 22%, 36%, 68% NDs + US, DOX-NDs, DOX-NDs + US, respectively, prolong survival tumor-bearing mice. Therefore, study demonstrates that combination chemotherapy promotes uniform treatment improve therapeutic efficacy. Statement Significance Tumor vasculature plays an important role proliferation by transporting oxygen nutrients. Previous studies inhibit growth ultrasound-stimulated microbubble destruction or vaporization. Although efficacy has been demonstrated; relative spatial distribution delivery, accompanied responses within solid tumors not discussed clearly. Herein, our drug-loaded chemical therapy. The vitro cytotoxicity, intravital imaging, histological assessment evaluate temporal cooperation between effect. These results some evidences complementary action explain high inhibition