Ultrasound Activated Nanobowls with Deep Penetration for Enhancing Sonodynamic Therapy of Orthotopic Liver Cancer

Owing to the high penetration ability and the safety of ultrasound (US) of sonodynamic therapy (SDT), it has gained significant attention in tumor treatment. However, its therapeutic efficiency depends on the performance of the sonosensitizers. The hypoxic microenvironment and abnormal stromal matrix restrict the full potential of sonosensitizers. In this study, a US-activated bowl-shaped nanobomb (APBN) is designed as a novel sonosensitizer to enhance the SDT effect through various means. This enhancement strategy combines three major characteristics: relieving tumor hypoxia, amplifying bubble cavitation damage, and US-movement-enhanced permeation. The unique bowl-shaped structure of APBN provides more favorable attachment sites for the generated oxygen gas bubbles. Thus, when catalase-like APBN catalyzes endogenous hydrogen peroxide to produce oxygen, bubbles accumulate at the groove, preventing the dissipation of oxygen and increasing the number of cavitation nuclei to improve the acoustic cavitation effect. This approach differs from traditional SDT strategies because it couples the sonodynamic effect with reactive oxygen species generation and bubble cavitation damage rather than a single action. Additionally, the asymmetric bowl-shaped structure generates a driving force under the US field, improving the distribution of sonosensitizers in the tumors. Using US and photoacoustic imaging for dual localization, these sonosensitizers can improve the accuracy of orthotopic liver tumor treatment, which presents a promising avenue for the treatment of deep tumors. A novel ultrasound (US)-movement bowl-shaped nanobomb (APBN), as a sonosensitizer, is designed to enhance the sonodynamic therapy effect by alleviating hypoxia, amplifying bubble cavitation damage, and US movement ability. Moreover, the localized plasmon resonance effect and bubble generation ability of APBN endow it with photoacoustic imaging and ultrasound imaging ability. This strategy presents a promising avenue for the treatment of deep tumors.image