Abstract Hepatocellular carcinoma (HCC) often arises from liver cirrhosis, yet real‐time, noninvasive monitoring of immune escape during this transition remains limited. We developed a multifunctional biomimetic nanoprobe (ICGB@Apt) by conjugating a programmed death‐ligand 1 (PD‐L1)–specific DNA aptamer (selected via Cell–SELEX) onto an indocyanine green/BMS‐684 polymer, enabling in vivo imaging and immune modulation. In CCl 4 ‐induced mouse models progressing from cirrhosis to HCC and in complementary in vitro 3D co‐culture systems, ICGB@Apt preferentially accumulated in tumor tissue, dynamically visualized PD‐L1, and mitigated disease progression. The probe enhanced CD8 + T‐cell activity (IFN‐γ and granzyme B), reduced fibrosis and tumor burden, and outperformed non‐aptamer controls (Apt+ICG or ICGB alone). Knockdown experiments and RNA‐seq highlighted the centrality of the programmed death‐1 (PD‐1)/PD‐L1 axis; immune deconvolution implicated CD8 + T cells, follicular helper T cells, and M0 macrophages in the cirrhosis‐to‐cancer shift. The nanoprobes showed favorable biocompatibility and enabled longitudinal tracking of primary and metastatic lesions. Together, these findings establish ICGB@Apt as a PD‐L1–targeted platform that simultaneously monitors and counteracts immune escape, offering translational potential for early detection and immunotherapy guidance in HCC.
Meng et al. (Sun,) studied this question.