Homology and Immune Checkpoint Dual-Targeted Sonocatalytic Nanoagents for Enhancing Sonodynamic Tumor Therapy.

Sonocatalytic nanoagents (SCNs), a kind of sonosensitizers, could catalyze oxygen to generate abundant reactive oxygen species (ROS) under stimulations of noninvasive and deep-penetrating ultrasound (US), which is commonly used for sonodynamic therapy (SDT) of tumors such as malignant melanoma. However, poor bioavailability of most SCNs and fast quenching of extracellular-generating ROS from SDT limit further applications of SCNs in the SDT of tumors. Herein, we synthesized a new kind of TiO2-based SCN functionalized with the malignant melanoma cell membrane (B16F10M) and programmed cell death-ligand 1 antibody (aPD-L1) for homology and immune checkpoint dual-targeted and enhanced sonodynamic tumor therapy. Under US irradiation, the synthesized SCN can catalytically generate a large amount of 1O2. In vitro experiments validate that functionalized SCNs exhibit precise targeting effects, high tumor cell uptake, and intracellular sonocatalytic killing of the B16F10 cells by a large amount of localized ROS. Utilizing the melanoma animal model, the functionalized SCN displays visible long-term retention in the tumor area, which assists the homology and immune checkpoint synergistically dual-targeted and enhanced in vivo SDT of the tumor. We suggest that this highly bioavailable and dual-functionalized SCN may provide a promising strategy and nanoplatform for enhancing sonodynamic tumor therapies.