Targeted Immunoimaging of Tumor-Associated Macrophages in Orthotopic Glioblastoma by the NIR-IIb Nanoprobes

Developing dynamic and highly sensitive methods for imaging M2-type tumor-associated macrophages (TAMs) is vital for monitoring the tumor progression and assessing the therapeutic efficacy. Here, the fabrication and application of rationally designed Er-based rare-earth nanoprobes for the targeted imaging of M2-type TAMs in glioblastoma (GBM) through the second near-infrared (NIR-II) fluorescence beyond 1500 nm is reported. The NIR-IIb fluorescence of Er-based rare-earth nanoparticles can be remarkably enhanced by optimizing their core-shell structures and the shell thickness, which allows for in vivo imaging under excitation by a 980 nm laser with the lowest power density (40 mW cm(-2)). These bright Er-based nanoparticles functionalized with M2pep polypeptide show notable targeting ability to M2-type macrophages, which has been well tested in both in vitro and in vivo experiments by their up-conversion (UC) fluorescence (540 nm) and down-shifting (DS) fluorescence (1525 nm), respectively. The targeting capability of these nanoprobes in vivo is also demonstrated by the overlap of immunofluorescence of M2-type TAMs and Arsenazo III staining of rare-earth ions in tumor tissue. It is envisioned that these nanoprobes can serve as a companion diagnostic tool to dynamically assess the progression and prognosis of GBM.

Automated summary

This study reports the development of a fluorescence imaging method using Er-based rare-earth nanoparticles for targeted imaging of M2-type tumor-associated macrophages (TAMs). By optimizing the core-shell structure and shell thickness, the fluorescence signal of the nanoparticles in the second near-infrared (NIR-IIb) range can be significantly enhanced, enabling high-sensitivity in vivo imaging. The nanoparticles functionalized with a targeting peptide show notable specificity in vitro and in vivo experiments, suggesting their potential as a diagnostic tool for assessing the progression and prognosis of glioblastoma.