Imaging of tumor-associated macrophages using near-infrared fluorophore-conjugated dextran-sulfate nanoparticles

Tumor-associated macrophage (TAM) imaging is critical to provide greater insight into cancer diagnosis and treatment, but current strategies to accomplish this are often inadequate. In this study, we prepared a TAM imaging probe by conjugating self-assembled dextran-sulfate nanoparticles (DSNPs) with a near-infrared (NIR) dye, Flamma^® 675 (FPR675). The FPR675-labeled DSNPs showed a spherical shape with a hydrodynamic size of 188 nm in the aqueous condition. Interestingly, exhibiting selective cellular uptake behavior mediated by macrophage scavenger receptor class A (SR-A), the FPR675-labeled DSNPs were shown to discriminate between cancer cells and macrophages and were preferentially taken up by TAMs. Furthermore, biocompatible FPR675-labeled DSNPs are favorable for whole-body NIR imaging. When systemically administered into tumor-bearing mice, these nanoprobes effectively accumulated in the tumor site. In immunohistochemistry, we also found that the SR-A-mediated targeting mechanism of the nanoprobes allowed for a robust visualization of TAMs present in the tumor microenvironment. Overall, these findings suggest that DS-based nanoprobes hold the potential for significant breakthroughs in the context of cancer theragnostics for TAM targeting. Graphical abstract: We developed biocompatible dextran-sulfate nanoparticles to evaluate the presence of tumor-associated macrophages (TAMs) in the tumor microenvironment. TAMs are known to play a critical role in the prognosis of cancer patients. To create the TAMs probe, we incorporated a fluorophore and 5β-cholanic acid into the dextran-sulfate polymer, resulting in the formation of spherical nanoparticles. These nanoparticles can serve as an effective tool for detecting TAMs in vivo. [Figure not available: see fulltext.]