Starlike polymer brush-based ultrasmall nanoparticles with simultaneously improved NIR-II fluorescence and blood circulation for efficient orthotopic glioblastoma imaging

Fluorescence imaging (FI) in the second near-infrared region (NIR-II, 1000–1700 nm) has attracted great attention for brain tumor imaging due to its deep penetration and high resolution. However, traditional NIR-II organic fluorescent nanoparticles (NPs) are usually hindered by uncontrolled large size (~30–100 nm), marked aggregation-caused quenching (ACQ) effect, and limited blood circulation (~1–3 h), which have great impact on efficient NIR-II FI of deep brain tumors. Herein, starlike polymer brush-based ultrasmall TQFP-10 NPs, with bright NIR-II fluorescence, prolonged blood circulation, and enhanced tumor accumulation, are facilely prepared for efficient orthotopic glioblastoma (GBM) imaging. Compared with traditional method prepared NPs (physically coated TQF@NPs and PEG modified TQF-PEG_5K NPs), the ultrasmall (~8 nm) TQFP-10 NPs display a higher NIR-II fluorescence QY (1.9%), which is 2.1- and 3.8-fold higher than TQF@NPs (0.9%) and TQF-PEG_5K NPs (0.5%), respectively. In addition, TQFP-10 NPs present a 10.6-fold higher blood circulation half-life (t_1/2 = 8.5 h) than that of TQF-PEG_5K NPs. Consequently, TQFP-10 NPs exhibit 4.2- and 33-fold higher maximal tumor to normal tissue ratio in subcutaneous and in situ NIR-II FI of GBM, respectively, than TQF@NPs and TQF-PEG_5K NPs, attractively realizing GBM imaging. This work provides a general strategy for constructing ultrasmall NIR-II fluorescent NPs with simultaneously improved NIR-II fluorescence and blood circulation for efficient brain tumor imaging.