Acoustically activated nanoplatforms achieve tumor regression by exacerbating tumor hypoxia.

Background: Rapid tumor proliferation can be mitigated by "starving the cancer cells" through nutrient and oxygen blood supply blockade to the tumor, which is a significant challenge in oncological treatment.

Methods: We developed a multipathway nano platform designed to improve hypoxia-exacerbated cancer starvation therapy. This was achieved by co-loading the acoustic sensitizer-IR780-and the vascular disruptor-vadimezan (DMXAA)-into dendritic silica nanocarriers to establish acid-responsive nanoplatforms, termed DMXAA/IR780@SiO2 (DIS NPs), using a simple one-pot synthesis method. In vivo and in vitro experiments were conducted to determine the antitumor mechanisms of this nanomaterial.

Results: In vitro cellular experiments revealed that reaching the acidic tumor microenvironment value with DMXAA/IR780@SiO2 degrades silica in DIS NPs, accompanied by the release of the drug, and the released DMXAA damaged blood vessels at the tumor site, thereby blocking oxygen and nutrient supplies. Concurrently, the acoustic sensitizer-IR780-released after the cleavage of DIS NPs generates reactive oxygen species under the action of ultrasound (US), thereby depleting oxygen, further aggravating tumor hypoxia, and damaging the mitochondria by disrupting the redox reaction, which ultimately triggers cellular damage and even death. Further, a significant therapeutic effect on tumors in vivo was observed when combined with ultrasound US therapy, demonstrating synergistic therapeutic effects in terms of acoustic dynamics and vascular disruption, as well as good biosafety.

Conclusion: The DIS NPs exhibit a promising approach for hypoxia-exacerbated cancer starvation therapy, providing a potential new avenue for cancer treatment with demonstrated efficacy and biocompatibility.