Tumor-associated macrophages (TAMs) play a crucial part in
cancer evolution. Dynamic imaging of TAMs is of great significance for treatment outcome evaluation and precision
tumor therapy. Currently, most fluorescence nanoprobes tend to accumulate in the liver and are difficult to metabolize, which leads to strong background signals and inadequate imaging quality of TAMs nearby the liver such as
pancreatic cancer. Herein, we aim to develop metabolizable
dextran-
indocyanine green (DN-ICG) nanoprobes in the second near-infrared window (NIR-II, 1 000-1 700 nm) for dynamic imaging of TAMs in
pancreatic cancer. Compared to free ICG, the NIR-II fluorescence intensity of DN-ICG nanoprobes increased by 279% with significantly improved stability. We demonstrated that DN-ICG nanoprobes could specifically target TAMs through the interaction of
dextran with specific ICAM-3-grabbing nonintegrin related 1 (SIGN-R1), which were highly expressed in TAMs. Subsequently, DN-ICG nanoprobes gradually metabolized in the liver yet remained in pancreatic
tumor stroma in mouse models, achieving a high signal-to-background ratio (SBR = 7) in deep tissue (∼0.5 cm) NIR-II imaging of TAMs. Moreover, DN-ICG nanoprobes could detect dynamic changes of TAMs induced by low-dose
radiotherapy and
zoledronic acid. Therefore, the highly biocompatible and biodegradable DN-ICG nanoprobes harbor great potential for precision
therapy in
pancreatic cancer.