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

Abstract

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.

Theranostic Nanoprobes with Aggregation‐Induced NIR‐II Emission: from Molecular Design to Biomedical Application

“…Bioimaging in the NIR-IIb range (1500-1700 nm, the longest wavelength in the NIR-II window) has demonstrated greater resolution, and deeper penetration depth than normal NIR-II fluorescence imaging, due to the extremely low scattering and almost disappeared autofluorescence in living body (Figure 1A and B). [43,88,89] However, due to the lack of a suitable molecular design strategy, the scientists are only able to extend the tail, rather than the peak, of fluorescence spectra of AIEgens into the NIR-IIb range. Even though, the advantages of their fluorescence imaging are still obvious by experiments.…”

Advances of NIR Light Responsive Materials for Diagnosis and Treatment of Brain Diseases

“…Moreover, the Er based NIR fluorescence probe was modified with M2pep polypeptide to target the M2-type tumor associated macrophages (TAMs) so as to realize the assessment of therapeutic efficacy of glioblastoma. [70] To achieve the NIR fluorescence imaging in vivo, they In addition, the NIR fluorescence imaging based on rare earth based luminescent materials can also be used for realtime evaluation of neuro inflammation (NI). Zhang et al developed the HOCl-responsive NIR fluorescence probes with NaYbF 4 : Gd@NaYF 4 : Yb, Tm (UCNPs) as energy donor, Cy-HOCl dye as quencher, and ANG peptide as targeting molecule for real-time tracking the progress of NI.…”

Development of functional nanomedicines for tumor associated macrophages-focused cancer immunotherapy

“…The assessment of Fe 3 O 4 NPs to predict patient treatment response by imaging TAMs using MRI technique is currently in clinical trials and is believed to be put into clinical practice in the near future 91 . In a study using NIR-II imaging by Zhu et al, they proposed a dynamic and highly sensitive approach for M2-TAMs imaging 141 . To be specific, an Er-based rare-earth NIR-IIb nanoprobes modified with M2pep polypeptide were rationally designed for targeted imaging of M2-TAMs in glioblastoma, which enabled in vivo imaging under 980 nm laser excitation and was verified that their targeted imaging capacity could be achieved by their up-conversion fluorescence (540 nm) and downshifting fluorescence (1525 nm).…”