Nanometer-Sized and Near-Infrared-II Fluorescent Extracellular Vesicles for Noninvasive High-Contrast Imaging of Tumors with High EGFR Expression

Fluorescence imaging in the second near-infrared (NIR-II) region possesses numerous advantages and shows a promising future in cancer imaging. Developing tumor-targeting NIR-II fluorescent probes with both high fluorescence brightness and favorable biocompatibility promotes the clinical applications of NIR-II fluorescence imaging technology. Herein, we used natural small extracellular vesicles with a size of 140 nm as a nanoplatform to integrate water-soluble NIR-II fluorescent CH1055-PEG molecules and epidermal growth factor receptor (EGFR)-targeting GE11 peptides to prepare a bright and biocompatible NIR-II fluorescent nanoprobe sEV-CH1055-GE11 for in vivo high-contrast imaging of tumors with high EGFR expression. Increased amounts of CH1055-PEG and nanoprobe modification with GE11 peptides enabled imaging with high NIR-II fluorescence brightness and enhanced tumor-targeting capability. In in vivo imaging, sEV-CH1055-GE11 achieved extremely high-contrast imaging of tumors with high EGFR expression. The tumor-to-background ratio surpassed the Rose criterion of 5 at 48 h post-injection and reached 10.43 at 72 h post-injection. Cell viability, blood analysis, and hematoxylin–eosin staining assays indicated that this nanoprobe possessed favorable biocompatibility. This study demonstrates the potential applications of sEV-CH1055-GE11 in NIR-II fluorescence imaging of tumors with high EGFR expression.