Miniature NIR-II Nanoprobes for Active-Targeted Phototheranostics of Brain Tumors.

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.