High-sensitivity PD-L1 immune checkpoint imaging in microtumors for immunotherapy using near-infrared persistent luminescence nanoparticles.

The efficacy of programmed cell death-ligand 1 (PD-L1)-based immune checkpoint blockade therapy (ICBT) depends on the tumor PD-L1 expression level. Accurate evaluation of tumor PD-L1 is essential to identify patients who will benefit most effectively and to develop appropriate treatment strategies. However, high-sensitivity evaluation of microtumor PD-L1 expression remains challenging in current ICBT landscape. Here, we develop a PD-L1-targeted near-infrared (NIR) persistent luminescence (PersL) nanoprobe, termed mZ-PD-L1, and establish a high-sensitivity PD-L1 imaging technique based on NIR PersL. This method allows high-sensitivity and precise imaging of PD-L1 in microtumors and micrometastases in vivo. mZ-PD-L1 exhibits biowindow-activated reproducible NIR PersL properties, along with exceptional PD-L1 targeting capability. By conducting in vivo NIR PersL imaging, mZ-PD-L1 facilitates high-sensitivity visualization of tumor PD-L1 expression. Using mZ-PD-L1, we achieve high-sensitivity and precise imaging of PD-L1 in microtumors (≤1 mm) and lymph node micrometastases, with imaging signal-to-background ratios as high as 27 and 37, respectively. This study provides a strategy to precisely and comprehensively evaluate PD-L1 in microtumors or micrometastases, significantly broadening the ICBT applications and offering a new method for personalized and precise ICBT.