Miniature NIR‐II Nanoprobes for Active‐Targeted Phototheranostics of Brain Tumors

Abstract Nanoprobes (NPs) in the second near‐infrared biowindow (NIR‐II, 1000–1700 nm) are developed and widely used in cancer phototheranostics. However, most NIR‐II NPs exhibit low phototheranostic efficiency due to their tedious synthetic routes, large particle sizes (>20 nm), and lack of active targeting properties. Here, miniature NIR‐II NPs, named HSA‐ICG‐iRGD, for active‐targeted NIR‐II phototheranostics of brain tumors are reported. The HSA‐ICG‐iRGD probes are designed based on hydrophobic interactions as well as hydrogen bonds between albumin and indocyanine green derivatives (ICG‐iRGD) via molecular docking. The as‐prepared NPs have a compact size of 10 nm and show tumor‐targeting ability by specifically binding to α v β 3 integrin receptors which are highly expressed on the surface of brain tumor cells via iRGD peptides. The HSA‐ICG‐iRGD NPs are then applied to perform active‐targeted NIR‐II fluorescence imaging, resulting in a signal‐to‐background ratio of 6.85 in orthotopic glioma mouse models. Under the selected laser irradiation of 808 nm, the photothermal effect of HSA‐ICG‐iRGD extends the survival of the tumor‐bearing mice to 55 days, significantly longer than that of the control group (30 days). These results highlight the potential of miniature NPs for active‐targeted NIR‐II fluorescence imaging and phototherapy of brain tumors.