Acidic tumor microenvironment-activated MRI nanoprobes for modulation and visualization of anti-PD-L1 immunotherapy

Tumor acidity has emerged as a pivotal regulator of immune checkpoint blockade (ICB). However, acidity-based therapy presents challenges of low efficiency and lack of reliable imaging technology for assessing the immune response. Here we report a magnetic resonance imaging (MRI)-guided ICB therapy (MRGIT) strategy to modulate and visualize the efficacy of anti-PD-L1 in pancreatic ductal adenocarcinoma (PDAC). MRGIT was achieved by a pH responsive nanoprobe (APPAM@U-104) composed of ultrasmall iron oxide nanoparticles (USIONs) and a tumor pH regulator (U-104). Notably, the nanoprobes exhibited a T1 "ON" MR signal in acidic tumors but switched to a T2 "ON" MR signal in a neutralized tumor microenvironment, resulting in a switchable MR signal from T1 to T2 during real-time MRI monitoring. Moreover, the switch of MR signals can serve as an indicator for alleviating tumor immune suppression, thus guiding the timing of anti-PD-L1 therapy. Our results revealed that the MRGIT strategy can potentiate the antitumor efficacy of anti-PD-L1 against pancreatic tumors. Collectively, this strategy sensitively regulates and recognizes tumor acidosis, thus paving the way for the modulation and noninvasive monitoring of anti-PD-L1 efficacy in PDAC.