Silver niobate/platinum piezoelectric heterojunction enhancing intra-tumoral infiltration of immune cells for transforming "cold tumor" into "hot tumor".

Cancer immunotherapy represents a promising strategy, however, its efficacy is often hindered by high tumor interstitial fluid pressure (TIFP) due to fluid retention, and strong solid stress (SS) caused by the excessive proliferation of cancer-associated fibroblasts (CAFs). These factors limit the infiltration of immune cells into the deeper layers of tumors, thereby reducing the efficacy of immunotherapy. In this study, we designed an innovative AgNbO3/Pt@HA (ANPH) Schottky heterojunction system to induce ultrasound (US)-triggered piezocatalytic reactions for cancer therapy, which catalyze the water decomposition in the tumor interstitial fluid to produce H2, therefore, resulting in a 48.16 % reduction in TIFP. Furthermore, the reactive oxygen species (ROS) generated by the system eliminated 59.4 % of CAFs, reducing the tumor extracellular matrix and SS by 44.07 %. This reduction facilitated a 3.95-fold and 3-fold increase in quantities of intratumoral CD8+ and CD4+ T cells, respectively, and transformed "cold tumors" into "hot tumors" to activate systemic immune responses. The growth of primary, distal, and metastatic tumors was significantly inhibited. This study demonstrates effective reductions in intratumoral TIFP and SS, promoting immune cell infiltration and thereby enhancing the efficacy of immunotherapy through US-triggered piezocatalytic reactions, which establishes a new paradigm of the application of nanocatalytic medicine.