Boosting TNBC immune checkpoint blockade with an imaging-therapy coupled ozone delivery nano system

[Display omitted] •Utilization of double imaging modes (ultrasound and MRI) for versatile diagnosis and evaluation.•Loading PFH enables ZSMT to carry ozone as ROS donor, after triggered by the ultrasound, PFH explodes as ultrasonic contrast agent and release ozone, and the TiO2-doped Mn-MOF catalyzes ozone into ROS.•Seamless integration of diagnostic and therapeutic approaches for tumors, facilitating “see-as-you-treat” strategy.•Bulk transcriptome sequencing reveals effective activation of CD8+ T cells in the tumor microenvironment following ultrasound-responsive ZSMTO and PD-1 blockade treatment. Synchronizing therapy and diagnosis is an ideal mode for clinical treatment of localized disease, e.g., tumor. Here, we develop a diagnosis-therapy coupled sonodynamic nano delivery system ZSMT which is constructed with a TiO2 embedding hollow Mn-MOF. Loaded with perfluorohexane, the ZSMT nanoparticle is not only capable for carrying ozone as a ROS donor but also endowed with double modes of imaging, namely ultrasound and magnetic resonance imaging. The TiO2-Mn-MOF can efficiently generate ROS by sonodynamic catalyzing ozone. Moreover, fluorescent tracer indicates the ZSMT particle can be internalized by tumor cells. With the stimulation of ultrasound, ozone carried ZSMT potently inhibits cell proliferation and promotes immunogenic cell death in vitro and in vivo by inducing a mitochondrial related cell death. Remarkably, combination of ultrasound-responsive ozone catalytic nano system and PD-1 blockade systematically suppresses the tumor growth by reprogramming the immune microenvironment. In conclusion, our sonodynamic nano system not only proves the principle of drug administration strategy on “treat-as-you-see” but also provides a combo regimen of improving PD-1 blockade with precision localized antigen boosting.